Manufacturing Technique of a Reflection Sample Holder for NIR and Raman Spectrophotometry

Abstract

Manufacturing techniques for sample holders (100, 110, 120, 140, 150) have been proposed. The sample holders are configured for spectrophotometric measurement of a sample (S) using a semi-transmissive semi-reflective technique. The sample holders include a sample receiving chamber (SRC) with a diffusive mirror (M). The curvature of the diffusive mirror (M) is adapted to the curvature of the surface of the sample (S) and / or to the curvature of the surface of a container (C) containing the sample (S). Further, a sample holder (160) for spectrophotometric measurement of a sample (S) using a transmission technique has been proposed. The sample holder includes a hollow light guiding channel (G), the inner wall of which is covered by a reflective coating (R), and is configured to at least partially wrap and / or surround a sample (S), such as a soft gel capsule, or a part of a container (C) containing the sample (S) along a convex portion of the sample (S) or the container (C).

Description

Technical Field

[0001] The present invention relates to any mechanism for spectroscopic measurement based on semi - transmission and semi - reflection of light, and more particularly to a sample receiving chamber having a reflective or mirror surface configured for such a mechanism.

[0002] Semi - transmission and semi - reflection is a development of the transmission technique. When a mirror is placed behind the sample, the light transmitted through the sample is reflected back to the sample and enters a diffuse reflection probe used as a detector. Thus, semi - transmission and semi - reflection measures a combination of transmission and reflection. This technique is applicable, for example, to emulsions, suspensions, gels, turbid liquids, and thus to various pharmaceutical intermediates, formulations and products, as well as crop products, foods, feeds, and is thus useful in related technologies.

[0003] In particular, semi - transmission and semi - reflection near - infrared spectroscopy enables the identification and / or quantification of active pharmaceutical ingredients (API), excipients, and / or the detection of product adulteration and / or sub - standard quality or API impurities, and the quantification / detection / verification of the physical properties (aggregation, particle size, etc.) of these components, regardless of whether they are in a liquid state within a sterile package or even a large amount of dry particles, such as dried medicinal plants. On the other hand, fruits, such as berries, cherries, or other plants or foods can also be analyzed without compromising their integrity. Thus, the proposed sample holder can also be used to determine the raw material or harvest date. Generally speaking, the proposed sample holder, and the proposed method using it, can thus also be associated with non - destructive testing.

[0004] Inappropriate production or storage of pharmaceutical products can result in the loss of the intended effect, or even harm to the organism to which the pharmaceutical product is applied.

[0005] Therefore, it is of utmost importance to control the quality and / or identity of pharmaceutical products before further use, for example, immediately before applying them to a patient or immediately before mixing them into an intermediate formulation.

[0006] Typically, when a sample of a batch of pharmaceutical products is taken and analyzed, the sample / batch is thereby destroyed. Since the batch size for individually produced infusion bags, pumps, or syringes is often n = 1, it is not possible to assess the quality of the preparation before batch release. Furthermore, these methods often require an analytical laboratory and trained highly specialized personnel to evaluate the analytical results, such as spectra or chromatograms.

Summary of the Invention

[0007] In view of the above, and in order not to compromise the integrity, and thus the sterility, of the original solution and / or its container, a reflective sample holder, a method for manufacturing the same, and a method for using the same are proposed.

[0008] In particular, by measuring the semi-transmission and semi-reflection of the measurement light beam (sample beam) of a NIR spectrophotometer or a Raman spectrophotometer directed through the sample, the information collected can be used to identify or even quantify the chemical components in the sample and / or analyze the physical properties of the sample. Such measurements can be performed simultaneously for various analytes, their parameters, and / or properties.

[0009] According to this embodiment, a sample holder is provided, which is specially configured by the shape of its sample receiving chamber, the surface structure of the diffusing mirror surface of the sample receiving chamber, and the reflectivity of the diffusing mirror surface for characterizing samples, such as pharmaceutical products, by NIR spectroscopy or Raman spectroscopy through semi-transmission and semi-reflection or even transmission. This sample holder makes it possible to improve the overall quality of the measurement results and the overall reproducibility.

[0010] The proposed sample receiving chamber comprising a NIR or Raman instrument, a sample, and a diffusive mirror is positioned relative to each other such that high-quality measurement results are ensured.

[0011] Surprisingly, additive manufacturing techniques may be adapted for the manufacture of various sample holders comprising a sample receiving chamber for pharmaceutical products, formulations, or other samples, each sample holder comprising at least a reflective surface that is either partially or fully covered with a diffusive mirror surface for use in semi-transmissive and semi-reflective measurements of the sample.

[0012] Alternatively, subtractive manufacturing processes may be used to manufacture the sample holders described herein that comprise a sample holding chamber having a diffusive mirror and / or a reflective coating, the curvature of the diffusive mirror and / or its reflective coating being adapted for semi-transmissive and semi-reflective measurements with pharmaceutical products, formulations, or other samples, such as for capsules, coated tablets, dried herbs, flower buds, or crops. Such various samples are very diverse in terms of their size and shape.

[0013] Thus, the selected manufacturing technique for producing corresponding diffusive mirrors whose curvature is adapted to the size and curvature, i.e., dimensions, of the sample to be measured must be very flexible. Modern CNC machines, i.e., machines generally understood as being based on computer numerical control, use computer-controlled machine tools to produce parts of defined shape from solid materials. They can be easily adapted to manufacture sample holders and diffusive mirrors of various shapes, each having a curvature adapted to the sample.

[0014] Removal manufacturing techniques suitable for producing a diffuser mirror having a curvature adapted to the curvature of the surface of the sample and / or the curvature of the surface of the container housing the sample include, by way of example, techniques such as turning, milling, boring, planing, drilling, reaming, electrical discharge machining (electroerosion), etching, photolithography, and laser ablation.

[0015] According to one embodiment, the sample receiving chamber of the sample holder is such that the diffuser mirror of the sample receiving chamber has a curvature adapted to the curvature of the surface of the sample and / or the curvature of the surface of the container containing the sample, and the diffuser mirror, in cross-section, can enclose and / or surround at least 30%, at least 50%, or even at least 75% of the surface of the sample and / or the surface of the container.

[0016] This can be achieved by the removal and / or additive manufacturing techniques described herein.

[0017] Furthermore, by using the proposed sample holder comprising a sample receiving chamber including a diffuser mirror and / or a reflective coating, a new method for characterizing, e.g., discriminating, verifying the conformity, semi-quantifying and quantifying medical caffeine-containing solutions with respect to their caffeine or other API content is established. The caffeine solution can be sterile or non-sterile. Usually, a syringe is used as the primary packaging of the caffeine solution. These medical caffeine solutions are used, for example, in the treatment of apnea in premature infants. By using the proposed sample holder, it becomes possible to perform a more simple, rapid and inexpensive characterization of various APIs with a reliability comparable to that of the methods used hitherto. Furthermore, by using the sample receiving chamber, it is ensured that the diffuser mirror does not come into direct contact with the sample and thus does not require cleaning.

Brief Description of the Drawings

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[0032] The complete disclosure of the present invention, including its best mode, enabling it to be practiced by those skilled in the art, is described more specifically in the remaining part of this specification, including reference to the accompanying drawings.

[0033] In the following detailed description, reference is made to the accompanying drawings, which form a part of this specification and in which specific embodiments and features of the invention are illustrated by way of example. It should be understood that other embodiments may be utilized and structural or logical changes may be made without departing from the scope of the present invention.

[0034] Accordingly, the following detailed description should not be construed in a limiting sense, and the scope of the present invention is defined by the appended claims.

Best Mode for Carrying Out the Invention

[0035] When used in conjunction with the term "comprising" in the claims and / or this specification, the use of the word "a" or "an" can mean "one", but it is also consistent with the meaning of "one or more", "at least one", and "one or more than one".

[0036] The use of the term "or" in the claims is used to mean "and / or" unless expressly indicated to refer only to an alternative or unless the alternative is mutually exclusive, but this disclosure supports definitions that refer only to an alternative and "and / or".

[0037] As used in this specification (above and below) and in the claims, the words "comprising" (and any form of comprising such as "comprise" and "comprises"), "having" (and any form of having such as "have" and "has"), "including" (and any form of including such as "includes" and "include"), or "containing" (and any form of containing such as "contains" and "contain") are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.

[0038] As used herein, the term "additive manufacturing" is different from subtractive techniques and includes techniques commonly applied to layers or beds containing specific particles or powders, such as fused deposition modeling (FDM), powder bed fusion (LPBF) techniques or variations thereof, e.g., Selective Laser Melting (SLM), Selective Laser Sintering (SLS), Electron Beam Melting (EBM), and Direct Metal Laser Sintering (DMLS), also known as such, which include metals, ceramics, and / or polymers; binder jetting or material jetting techniques using particles containing polymers, ceramics, or metals or alloys; material extrusion techniques in which material is drawn through an optionally heated nozzle, including continuously depositing the extruded material; and wire arc melting techniques including melting the metal within an electric arc. Further, lost wax casting is also considered an additive manufacturing technique. Further, herein, injection molding is also considered an additive manufacturing technique. Thus, the technique for producing the proposed reflective sample holder with a sample receiving chamber includes at least one of the additive manufacturing techniques mentioned, or a combination of the additive manufacturing techniques mentioned. Advantageously, additive manufacturing is usually very flexible and allows for easy adaptation of the components of the proposed sample holder, particularly the sample receiving chamber it comprises, and / or the mirror surface thereof or within it, e.g., size, shape, and surface structure.

[0039] As mentioned above, subtractive manufacturing methods may also be used to produce the sample holders described herein with their diffusive mirrors, and the curvature of the diffusive mirror is designed to correspond to the curvature of the surface of the sample to be measured. Advantageously, in addition to the possibility of generating models useful for manufacturing molds, subtractive manufacturing also allows for directly manufacturing sample holders with diffusive mirrors having a conforming curvature.

[0040] The alternative expression "the curvature of the diffusing mirror is adapted to the curvature of the surface of the sample and / or the surface of the container for the sample" is intended to explain, for example, that when the sample is held by a sample holder, the distance obtained between the corresponding surfaces of the diffusing mirror and the sample is usually uniform. Advantageously, this enables the semi-transmissive and semi-reflective light of the sample, which can be, for example, a dragee or a suppository and whose shape can vary depending on the manufacturer, to be measured accurately and reproducibly.

[0041] At least the surface of the sample receiving chamber is covered either partially or completely by a reflective surface and comprises the diffusing mirror and / or reflective coating mentioned. The reflective material and the corresponding deposition technique can be selected from, by way of example, chemical vapor deposition technique (CVD), physical vapor deposition technique (PVD), vacuum evaporation technique, plating (electroless and galvanic), and atomic layer deposition (ALD).

[0042] Advantageously, the reflective material is gold, steel, aluminum, or any other NIR reflective material, such as Teflon® or an alloy comprising at least one of these materials. The convenient wavenumber range of the measurement light beam, i.e., the sample beam, corresponds to a wavelength range from 800 nm to 2.5 μm, 4,000 - 12,500 cm -1 -1.

[0043] According to a typical embodiment, the surface of the sample holder directed towards the sample is reflective to NIR. The sample holder, particularly its sample receiving chamber, encloses the sample as a whole or at least along the circumferential direction of the tubular part of the container that protects the sample from contamination.

[0044] The described reflective surface can give rise to an integrating sphere, and although the shape of the sample receiving chamber may differ from an ideal sphere, it can be referred to as an integrating sphere (Ulbricht sphere).

[0045] The proposed reflective sample holder, in particular its sample receiving chamber, due to its shape, its size, its reflective surface, the material used for the reflective surface, the diffuser mirror that can partially or completely cover the reflective surface, and the geometry and / or shape of the surface of the diffuser mirror, is configured to spectrophotometrically measure samples such as pharmaceutical formulations, their components, and products mentioned above using semi-transmissive semi-reflective NIR spectrophotometry and / or semi-transmissive semi-reflective Raman spectrophotometry regardless of their shape, size, or viscosity, e.g., viscosity.

[0046] The geometry and / or shape of the surface of the diffuser mirror is constituted by a flat, curved, or any other surface including geometric bodies such as pyramids, or inclined separate surfaces such as triangles (e.g., in the case of these pyramids). These geometric bodies may be arranged adjacent to each other, i.e., next to each other, or at a distance from each other, and can form several adjacent rows arranged either adjacent to each other or at equal or gradually changing distances from each other. The result can be, for example, a parametric geometry. These surfaces may or may not be polished, partially polished, or unpolished. With the described configuration, the reflectivity of the diffuser mirror, and thus the overall reflectivity of the reflective sample holder, in particular its sample receiving chamber (SRC), is determined. Usually, the resulting corrugated surface is coated with a reflective layer, e.g., a gold layer.

[0047] For practical reasons, the reflection sample holder described in this specification is compared by measurement experiments with a generally commercially available reflective gold mirror having a similar high reflectivity. Importantly, generally available reflective gold mirrors are limited to flat, i.e., planar surfaces. For these and other reasons, it becomes possible to increase the overall quality of the measurement results and the overall reproducibility by the reflection sample holder proposed in this specification. In particular, the technical effects achieved with respect to the obtained measurement results are a higher signal-to-noise ratio, a higher spectral resolution, and thus an improved detection limit (limit of detection: LOD) and sensitivity compared to generally available reflective gold mirrors of similar reflectivity, and furthermore, improved reproducibility.

[0048] As used herein, the term "sample" includes any natural product (plant extract, dried plant, and the like), any pharmaceutical preparation, any liquid, any solution, any dispersion, any solid (e.g., powder, lyophilizate, and the like), any two-phase system, whether partially or completely enclosed or not enclosed by a container. Examples of such containers are syringes, infusion bags, vials, bottles, cuvettes, blisters, or any other container. The primary container can be partially or completely enclosed by a second container.

[0049] As used herein, the term "semi-solid" includes gels, hydrogels, pastes, or lotions (having a higher viscosity compared to normal physiological (aqueous) solutions and thus mostly being a solid / liquid or liquid / liquid two-phase system). This term is used in a form corresponding to its general understanding by those skilled in the pharmaceutical and / or food technology arts.

[0050] Furthermore, it should be noted that the term "solution" as used herein is not limited to aqueous solutions and may also relate to other solvents, such as oils. Thus, the liquid compositions that can be measured using the proposed reflection sample holder include solutions and dispersions and can consist of, for example, multi-component / multi-phase systems (foams, emulsions, aerosols). The solution may be sterile or non-sterile.

[0051] Regarding pharmaceutical formulations containing soft or hard gelatin capsules, dragees, suppositories, tablets, or film-coated tablets that are characterized using a reflection sample holder, they may contain a liquid medium and a pharmaceutically active ingredient (API) dissolved or dispersed therein. Thus, they may contain an API and a liquid excipient. However, the excipient may be solid or may contain solid particles.

[0052] For the purposes of the present application, the term "pharmaceutical formulation" is intended to describe any pharmaceutical dosage form known to those skilled in the art for transporting a pharmaceutically active compound into the body of a human or animal in order to achieve its desired therapeutic and / or diagnostic effect. Usually, a pharmaceutical dosage form contains a mixture of a drug component, i.e., a pharmaceutically active ingredient, and a non-drug component (i.e., an excipient). Generally, these pharmaceutical dosage forms can be classified by various aspects, such as their route of administration (e.g., oral, inhalation, parenteral, topical administration, more specifically ophthalmic drug administration), or their physical appearance (e.g., solid, semi-solid, liquid, gas). For the purposes of the present application, in particular, these solid, semi-solid, or liquid dosage forms that can be administered locally, parenterally by injection, or orally are used. For example, such dosage forms include ointments, creams, gels, lotions, dispersions, granules, solutions or sterile solutions, or injection solutions or infusions, soft or hard gelatin capsules, dragees, suppositories, tablets, or film-coated tablets, which are intended to be a non-exhaustive list of possible dosage forms.

[0053] According to one embodiment that can be combined with any of the other embodiments described herein, the pharmaceutical formulation comprises an intermediate composition. The concentration of the intermediate composition can be from 0.1% w / w to 99.9% w / w, particularly from 1% w / w to 99% w / w, particularly from 2.5% w / w to 90% w / w, particularly from 5% w / w to 80% w / w, more specifically from 10% w / w to 60% w / w, more specifically from 15% w / w to 40% w / w, based on the total weight of the pharmaceutical formulation.

[0054] Furthermore, the concentration of the intermediate composition can be from 10% w / w to 45% w / w, particularly from 20% w / w to 40% w / w, more specifically from 30% w / w to 38% w / w, based on the total weight of the pharmaceutical formulation. Also, the concentration of the intermediate composition can be from 1% w / w to 30% w / w, particularly from 5% w / w to 25% w / w, more specifically from 10% w / w to 20% w / w, based on the total weight of the pharmaceutical formulation. Also, the concentration of the intermediate composition can be from 0.1% w / w to 15% w / w, particularly from 1% w / w to 10% w / w, more specifically from 2% w / w to 5% w / w, based on the total weight of the pharmaceutical formulation.

[0055] According to one embodiment that can be combined with any of the other embodiments described herein, the pharmaceutical composition further comprises a liquid medium.

[0056] According to one embodiment that can be combined with any of the other embodiments described herein, the liquid medium in the sample is an aqueous solution such as phosphate buffer saline (PBS), water such as aqua ad injectabilia, glycerol, or an oil selected from hemp oil, castor oil, clove oil, cassia oil, almond oil, corn oil, sesame oil, peanut oil, cottonseed oil, safflower oil, corn oil, linseed oil, rapeseed oil, soybean oil, caraway oil, rosemary oil, peanut oil, peppermint oil, sunflower oil, eucalyptus oil, olive oil, perilla oil, peppermint oil, eucalyptus oil, bergamot oil, anise oil, fennel oil, or rose oil. These liquid media can be used alone or in any combination of two or more of them. The concentration of the liquid medium can be from 1% w / w to 99.9% w / w, particularly from 5% w / w to 95% w / w, particularly from 10% w / w to 90% w / w, particularly from 20% w / w to 80% w / w, more specifically from 30% w / w to 70% w / w, based on the total weight of the pharmaceutical formulation.

[0057] According to certain embodiments, the pharmaceutical component that is characterized with respect to its pharmaceutically important constituents using the proposed sample receiving chamber is a pharmaceutical caffeine solution. The pharmaceutical caffeine solution is used in the treatment of apnea in premature infants. However, such solutions must be sterile, and non-destructive analytical methods that can verify the quality of the manufactured or stored pharmaceutical caffeine solution are not currently available. All generally available analytical methods either destroy the sample or carry a risk of contaminating the sample and thus losing the sterility of the sample. The main difficulty is to analyze the pharmaceutical caffeine solution while it is still contained within its primary packaging, for example a syringe. However, due to its shape, the material it is made of, and the thickness of the material, the syringe makes it impossible to analyze the contained solution using currently available methods. By using the proposed reflective sample holder with a sample receiving chamber, it becomes possible to characterize the caffeine in the pharmaceutical caffeine solution, for example, identify it, verify its compliance, semi-quantify and quantify it.

[0058] Also, the concentration of the pharmaceutical caffeine solution can be a liquid medium of from 0.05% w / w to 30% w / w, particularly from 0.25% w / w to 15% w / w, more specifically from 0.5% w / w to 1.5% w / w, based on the total weight of the pharmaceutical formulation.

[0059] According to certain embodiments, the pharmaceutical component to be characterized with respect to its pharmaceutically important constituents using the proposed sample receiving chamber is a cannabis extract. The extract from cannabis can be contained within any container, more specifically within a vial or syringe. At present, it is not possible to identify or quantify, in a simple and rapid manner, the content of, for example, cannabidiol (CBD) and tetrahydrocannabinol (THC) in extracts from cannabis in medical cannabis preparations. One of the techniques used to date is HPLC, which requires a dedicated laboratory environment and highly skilled personnel. As major cannabinoids, in addition to CBD and THC, other substances that can be detected with high reliability using, for example, NIR spectroscopy with the proposed reflection sample holder are cannabidiol acid (CBDA), tetrahydrocannabinolic acid (THCA), cannabinol (CBN), cannabigerol (CBG), cannabigerolic acid (CBGA), cannabichromevarin (CBCV), cannabichromen (CBC), cannabicyclol (CBL), cannabielsoin (CBE), cannabinodiol (CBND), cannabitriol (CBTL), cannabidivarin (CBDV), and tetrahydrocannabivarin (THCV).

[0060] Also, the concentration of the liquid medium can be from 0.05% w / w to 99.9% w / w, particularly from 0.5% w / w to 50% w / w, more specifically from 0.75% w / w to 20% w / w, and even more specifically from 1% w / w to 10% w / w of the liquid medium, based on the total weight of the pharmaceutical formulation.

[0061] According to one embodiment that can be combined with any of the other embodiments described herein, the pharmaceutical preparation mentioned above is a dispersion comprising the pharmaceutical preparation as the dispersed phase and a liquid medium as the dispersant. Further, the dispersed phase can be a colloidal dispersed phase. For the purposes of the present application, the term "colloidal dispersed phase" in relation to a pharmaceutical preparation means that the dispersed phase has a particle size of from 1 μm to 500 μm, particularly from 10 μm to 300 μm, more specifically from 50 μm to 200 μm.

[0062] According to one embodiment that can be combined with any of the other embodiments described herein, the dispersion is a gel, a suspension, a foam, or an emulsion.

[0063] Generally, a reflection sample holder for spectrophotometric measurement of a sample by semi - transmission semi - reflection and / or transmission is proposed. This comprises a sample receiving chamber, which is constituted by its shape, its size, the reflection surface and / or the surface structure of at least a part of the reflection surface, and the material used for the reflection surface, in particular the material of its diffusive mirror surface that partially or completely covers the reflection surface, and the geometry and / or shape of the surface of the diffusive mirror for various samples and sample geometries. The reflection sample holder described herein is compared by measurement experiments with a generally available reflection gold mirror having a similar high reflectivity. Importantly, the generally available reflection gold mirror is limited to a flat surface.

[0064] In particular, according to one embodiment, a sample holder for spectrophotometric measurement of a sample using a semi - transmission semi - reflection technique is proposed. The sample holder comprises a sample receiving chamber with a diffusive mirror. The curvature of the diffusive mirror is adapted to the curvature of the surface of the sample and / or to the curvature of the surface of the container containing the sample.

[0065] Advantageously, the reflection sample holder described herein enables a higher overall quality of the measurement results and a higher overall reproducibility. More specifically, using the reflection sample holder enables a higher signal-to-noise ratio, a higher spectral resolution, and thus improved detection limits and sensitivity. Further, the reproducibility of the measurement is significantly improved.

[0066] According to one embodiment, the proposed sample holder comprises a hollow light guiding channel. In this hollow channel, the fluid inside the channel is typically ambient air or gas and not a liquid or solid as is commonly used in optical fibers or waveguides. Unlike optical fibers and optical waveguides, the cross-sectional shape and / or its diameter vary along the length of the light guiding channel and are adapted to the shape of the sample. The light guiding channel partially or completely surrounds the sample and / or the container. Further, the light guiding channel can also be adapted to be optically connected to the measurement window of the spectrophotometer or the detector of the spectrophotometer, such as an integrating sphere inside the spectrophotometer.

[0067] Advantageously, signal loss can be significantly minimized and the sensitivity of Raman and / or NIR measurements of the sample can be increased.

[0068] According to one embodiment, the sample holder is configured for spectrophotometric measurement of a sample using a transmission technique and / or a semi-transmissive semi-reflective technique by means of a hollow light guiding channel optically connected to a sample receiving chamber, and the inner wall of the hollow light guiding channel is covered with a smooth reflective coating. The light guiding channel is configured to at least partially enclose a part of the sample or a part of the container containing the sample. Typically, a part of the light guiding channel is positioned covering or adjacent to a surface of a part of the sample or the container, more preferably along the circumferential direction of the curved surface of the sample or the container. Further, the light guiding channel can also be adapted to be optically connected to the measurement window of the spectrophotometer or the detector of the spectrophotometer, such as an integrating sphere inside or even outside the spectrophotometer.

[0069] Therein, a part of the sample and / or the container can be tubular (e.g., having a circular cross-section).

[0070] Advantageously, the sample holder is adapted to any size or shape of a flexible or non-flexible container that houses the analyte, depending on the size and shape of its sample receiving chamber.

[0071] According to one embodiment, the shape of the sample receiving chamber is configured to receive a container containing the sample, where the container represents either the primary container of the sample and a single storage container, i.e., the primary container, or the container represents a secondary container that encloses the primary container, and the sample is disposed within the primary container. Usually, the container is a closed, bacteriostatic container that provides a barrier against any contamination of the sample, e.g., contamination by liquids, dust, viruses, and microorganisms or their spores.

[0072] The advantages were mentioned in the introduction of this application.

[0073] According to one embodiment, the container includes at least one of plastic, paper, glass, metal, and fiber products, e.g., non-woven fabrics; the paper and fiber products can optionally be coated with a polymer to ensure the sterility of the volume enclosed by the container. Optionally, the plastic is selected from thermoformed polymer films, polymer shrink films, and plastic film bags.

[0074] Advantageously, the measurement signal generated by the container and its material does not interfere with the signal obtained from the analyte. These containers ensure the sterility of the sample, e.g., the sterility of pharmaceutical preparations.

[0075] According to one embodiment, the sample receiving chamber completely encloses the sample as a whole, or at least encloses the sample along the circumferential direction of the curved or even circular surface of the sample or the container, or the tubular portion of the sample or the container containing it.

[0076] Advantageously, signal loss can be minimized and signal strength increased to improve the sensitivity of a method for detecting an analyte, such as a pharmaceutically active substance.

[0077] According to one embodiment, the inner surface of the channel wall of the light guiding channel is at least partially covered with a reflective coating, and the reflective coating is reflective with respect to the light used in the measurement light beam used in spectrophotometry. Therein, the material used as the reflective coating is selected from metals, glasses, ceramics, and polymers such as Teflon. Usually, the reflective coating material is reflective with respect to NIR within the wavelength range used.

[0078] According to one embodiment, the sample to which the sample holder is adapted or used can be formed into a solid such as a crop, fruit, flower bud, flower part, plant extract, vegetable oil, powder or powder mixture, and the pharmaceutical dosage form selected from the following: tablets, coated tablets, suppositories, coated suppositories, hard gelatin capsules, soft gelatin capsules, candies, drops, ointments, creams, gels, lotions, dispersions, granules, solutions, injection solutions, infusions, especially enteral feeding formulas, liquid diets.

[0079] Advantageously, these are typical dosage forms of pharmaceutically active ingredients administered to patients.

[0080] According to one embodiment, the container is selected from syringes, infusion bags, vials, bottles, cuvettes, blisters, hard or soft gelatin capsules, films of film-coated tablets, dragees, suppositories, and film-coated suppositories.

[0081] According to one embodiment, at least a portion of the sample receiving chamber includes one of a cylinder, tube, sphere, hemisphere, prolate spheroid, oblate spheroid, ellipsoid, ellipse, paraboloid, cube, cuboid, prism, pyramid, cone, frustum of a cone, hyperboloid, parabolic shape, helix, torus, parametric geometry, and differential geometry.

[0082] Advantageously, the corresponding shape of the sample receiving chamber or at least a part thereof is adapted to optimally fit the sample within the sample receiving chamber, thus achieving a higher overall quality of the measurement and a higher overall reproducibility.

[0083] According to one embodiment, the surface structure of the diffusing mirror includes a plurality of geometric bodies or parts thereof, and the geometric bodies are selected from cylinders; tubes; spheres; hemispheres; prolate spheroids; oblate spheroids; ellipsoids; ellipses; paraboloids; cubes; cuboids; prisms, especially oblique prisms, more specifically triangular or quadrilateral or pentagonal or hexagonal oblique prisms, especially oblique triangular prisms. The geometric bodies can also be selected from pyramids, more specifically oblique pyramids and / or right pyramids, even more specifically triangular, quadrilateral, pentagonal, or hexagonal oblique pyramids and / or right pyramids. These can also be selected from cones, frustums of cones, hyperboloids, parabolic shapes, helicoids (or a plurality of helicoids), and tori (or a plurality of tori). According to typical embodiments, these geometric bodies are arranged adjacent to each other, that is, directly adjacent to each other, or at a certain distance from each other. There, the above distance may gradually change along a row of such geometric bodies and / or parts thereof, and the above row can be either adjacent to each other or arranged at a distance from each other.

[0084] According to one embodiment, the sample holder further comprises an identification element, which is optically or electronically readable and is configured to provide information selected from the type of sample to be accommodated (such as a syringe or an infusion bag), the sample holder ID, the length of the optical path, the type of the surface structure of the diffusing mirror (M), the diameter of the measurable sample; and / or the shape of the measurable sample.

[0085] According to one embodiment, the identification element includes 2D codes such as barcodes or QR codes (registered trademarks); RFID and / or holograms.

[0086] According to one embodiment, a manufacturing technique for producing the proposed sample holder is disclosed, the manufacturing technique at least including an additive manufacturing technique selected from 3D printing of at least a partial wax model of the sample holder; and application of lost wax casting, the lost wax casting including casting of molten metal, molten metal alloy, and / or molten IR reflective polymer such as Teflon.

[0087] According to another embodiment, a manufacturing method for producing the proposed sample holder is disclosed, including an additive manufacturing method and / or a subtractive manufacturing method. The subtractive manufacturing method preferably includes the following: turning, milling, boring, planing, drilling, reaming, grinding, electrical discharge machining, photolithography, etching, and laser ablation, such as femtosecond laser ablation, including at least one of the CNC methods. The subtractive process can be used to create, for example, a wax model for the lost wax process, or directly fabricate a sample holder and / or its diffusion mirror having a surface whose curvature is matched to the curvature of the surface of the sample. The material to be processed can be selected from wax, such as wax containing beeswax, polymers, such as Teflon (PTFE), metals, alloys, and ceramics. If the reflectivity of the substrate, such as metal, is not sufficient, this surface can be additionally coated with a reflective material, such as gold. In other words, by using subtractive manufacturing, a sample holder with a diffusion mirror or a blank of a sample holder with a diffusion mirror can be manufactured. Therein, the material of the sample holder or its blank is usually selected from polymers, copolymers, polymer mixtures, metals, alloys, minerals, and ceramics. To obtain the desired reflectivity of the surface of the sample holder facing the sample and / or to produce a diffusion mirror, a coating, such as a gold layer, can be applied. Applicable coating techniques include PVD, CVD, and plating. Depending on the shape and / or size of the sample, the manufacturing method (technique) can include forming or deformation techniques such as rubber pad forming and deep drawing. These techniques are particularly useful for fabricating a sample holder having a diffusion mirror with a concave shape adapted for measuring individual samples such as soft gel capsules having an oval, round, elliptical, or suppository shape; suppositories; tabs; twist-offs; or soft gel capsules or pills having a special shape such as a star or any other shape. Preferably, when viewed in cross-section, the diffusion mirror encloses and / or surrounds at least 30%, or even up to 50%, of the cross-sectional surface of the sample and / or the cross-sectional surface of the container containing the sample.Advantageously, a representative semi-transmissive semi-reflective signal is collected by realizing the correspondence between the surface of the mirror and the surface of the sample and / or the container containing the sample. This enables precise measurements using NIR or Raman spectrophotometry.

[0088] According to one embodiment, a manufacturing technique for producing a sample holder configured for spectrophotometric measurement of a sample using a semi-transmissive semi-reflective technique is proposed. In this case, the sample holder includes a sample receiving chamber containing a diffusive mirror. The curvature of the diffusive mirror is adapted to the curvature of the surface of the sample and / or the curvature of the surface of the container containing the sample. The proposed manufacturing technique includes a subtractive manufacturing technique.

[0089] Advantageously, the subtractive manufacturing process is well established. The corresponding machines and tools are readily accessible to those skilled in the art, typically factory technicians. These techniques are applicable according to the scale of typical samples to be measured. Usually, the samples to be measured reach a maximum dimension of up to a few centimeters. The subtractive manufacturing process can typically achieve an accuracy of 1 to several μm (micrometers) or mm (millimeters). It goes without saying that the subtractive manufacturing technique can achieve an accuracy (precision) of μm or mm even at a size scale of several dm (decimeters) or m (meters). For example, precision machining photolithography or laser ablation can achieve an accuracy of less than 1 μm, which is a sub-micrometer precision, and is advantageous for fabricating diffusive mirrors for semi-transmissive semi-reflective measurements.

[0090] According to one embodiment, a manufacturing technique for producing a sample holder configured for spectrophotometric measurement of a sample using a semi-transmissive semi-reflective technique is proposed. The manufacturing technique includes a step of manufacturing a sample receiving chamber of the sample holder such that the sample receiving chamber is provided with a diffusive mirror. The curvature of the diffusive mirror is adapted to the curvature of the surface of the sample and / or the curvature of the surface of the container containing the sample. In cross-section, the diffusive mirror is adapted to enclose and / or surround at least about 30% of the surface of the sample and / or the surface of the container.

[0091] In other words, along the outer line of the cross-section, at least 30% of the length of the outer line is covered (matched, repeated, or fitted) by the curvature of the diffusive mirror. Stated in another way, the curvature of the diffusive mirror corresponds to the corresponding curvature of the sample and / or the container over a length of at least 30% of the outer contour length of the cross-section of at least the sample or the container containing the sample. Such matching and fitting enables the collection of a representative semi-transmissive semi-reflective signal from the sample, regardless of whether the sample is enclosed within the container or not.

[0092] According to one embodiment, in cross-section, the diffusive mirror is adapted to enclose and / or surround at least about 50%, or even at least about 75% of the surface of the sample and / or the surface of the container. Here, the expression "about" is intended to include ±5%.

[0093] Advantageously, the achievable precision of the semi-transmissive semi-reflective measurement is enhanced by the indicated range of at least 45 - 55% corresponding to the indicated value of at least about 50%. The indicated range of at least about 75% corresponds to a range of at least 70% - 80% of the length of the contour of the cross-section. Such high values further increase the achievable precision of the semi-transmissive semi-reflective measurement.

[0094] According to one embodiment, the manufacturing technique of the sample receiving chamber includes at least one of a subtractive manufacturing technique and an additive manufacturing technique.

[0095] Advantageously, modern additive and subtractive manufacturing are well-established techniques applicable to the relevant size scales.

[0096] According to one embodiment, the subtractive manufacturing technique is used for the manufacture of the diffuser mirror.

[0097] Advantageously, the repetitive fine structure of the diffuser mirror can be easily realized.

[0098] According to one embodiment, the subtractive manufacturing technique is selected from turning, milling, boring, facing, drilling, reaming, grinding, electrical discharge machining, electro-erosion, etching, photolithography, and laser ablation.

[0099] These are readily accessible and thus available techniques.

[0100] According to one embodiment, the manufacturing technique includes CNC machining.

[0101] Among the advantages of the CNC technique are, inter alia, high precision and high reproducibility.

[0102] According to one embodiment, the CNC machining includes at least one of turning, milling, boring, facing, drilling, and grinding.

[0103] According to one embodiment, the subtractive manufacturing technique is applied to materials selected from wax, polymer, metal, alloy, and ceramic.

[0104] Advantageously, these materials are well-suited for subtractive manufacturing, enabling the obtaining of a properly microstructured surface with a defined curvature.

[0105] According to one embodiment, the proposed manufacturing technique further includes an additive manufacturing technique.

[0106] Advantageously, the combination of additive and subtractive manufacturing techniques enables obtaining any shape and structure of the diffuser mirror, and thus the diffuser mirror can be adapted to the curvature of the sample and / or the curvature of the container containing the sample.

[0107] According to one embodiment, the proposed manufacturing technique comprises the process steps: providing a blank; providing a first digital data set, the first digital data set describing the shape and / or curvature of the surface of the sample; generating a second digital data set from the first digital data set; the second digital data set describing at least the shape and / or curvature of the diffuser mirror of the sample holder comprising the diffuser mirror; applying the second data set to numerically control the movement and / or operation of a machine tool, wherein the tool forms at least a part of the sample holder from the blank.

[0108] Advantageously, the corresponding part of the sample holder is made using a machine starting from the blank and is thus homogeneous. The curvature and surface structure of the diffuser mirror can be easily adapted to the dimensions and shape of the sample by modifying the digital data set.

[0109] According to one embodiment, a part of the sample holder produced by the manufacturing technique mentioned above using the above machine and including the above tool is a diffuser mirror.

[0110] As previously explained, the diffuser mirror is configured to reproducibly collect a representative semi-transmissive semi-reflective signal from the sample held inside / by the sample holder / sample receiving chamber.

[0111] According to one embodiment, the machine used is a CNC machine.

[0112] The advantages of CNC machining are well known and, for example, by simply adapting the corresponding digital data set, it is easily adaptable to produce sample holders and diffusion mirrors of various shapes, each having a curvature that matches the current batch of samples.

[0113] According to one embodiment, the step of providing the first digital data set preferably includes the steps of digitally scanning the sample to be measured by 3D laser scanning techniques and obtaining a digital representation of the sample.

[0114] According to one embodiment, the second digital data set is based on or corresponds to a data set obtainable using slicing software.

[0115] According to one embodiment, the second digital data set is obtained from the first digital data set by scaling the radius of curvature of the curvature of the surface of the sample.

[0116] Advantageously, this scaling enables the shape, curvature, and size of the mirror to be easily adapted to another sample having a different size and / or shape and thus a different curvature of the sample surface. Thus, a sample holder with a diffusion mirror can be easily configured to match, for example, any selected type of sample to be measured, such as suppositories of various shapes, tablets of various sizes and shapes, tabs, pre-filled syringes, etc.

[0117] According to one embodiment, the proposed manufacturing technique includes a coating step for producing a reflective layer, and the coating step is selected in particular from galvanic plating, electroless plating, chemical vapor deposition, and physical vapor deposition of a gold layer.

[0118] These coating techniques make it possible to deposit reflective materials such as, for example, gold, Teflon, platinum, silver, copper, nickel smoothly and uniformly.

[0119] According to one embodiment, a sample holder configured for spectrophotometric measurement of a sample using a semi-transmissive semi-reflective technique is proposed, the sample holder comprising a sample receiving chamber having a diffusing mirror, the curvature of the diffusing mirror being adapted to the curvature and / or shape of the surface of the sample and / or to the curvature of the surface of the container containing the sample, and at least a part of the sample holder including the diffusing mirror being produced using a manufacturing technique according to any of the previous embodiments, and / or the diffusing mirror being adapted to enclose and / or surround at least 30% of the surface of the sample (S) and / or of the surface of the container in cross-section.

[0120] The advantages are obvious.

[0121] According to one embodiment, a part of the sample holder including the diffusing mirror is the diffusing mirror.

[0122] According to one embodiment, lost wax casting includes generating a casting mold for a portion of the sample holder by embedding a 3D printed wax model, and the embedding may include providing a path for the molten wax to flow and air to exit the casting mold. Lost wax casting further includes generating a mold by covering the wax model with a mold forming material, which is typically selected from silica slurry, ceramic slip, and stucco. Application of these techniques and drying of the resulting green body result in a green shell. The green body / green shell is heated, burnout, and usually sintered to a solid, i.e., a hard and stable mold, while the wax melts and leaves the shell and / or mold. The mold is then used for casting by pouring molten metal or a molten metal alloy into the mold. The mold can also be used, for example, in injection molding using a molten polymer. Finally, the casting is released or removed from the mold. Removal may include breaking the shell / mold. The removed (raw) casting is further finished, and finishing includes at least one of grinding, polishing, plating, electroplating, and / or deposition of a reflective layer, particularly a gold layer.

[0123] Advantageously, the molten wax technique is well established and can be adapted to any shape or surface structure of the proposed elements of the sample holder. Further, as previously mentioned, gold reflects more than 95 percent of the incident radiation at wavelengths above 700 nm. Therefore, the intensity of the original light beam lost during semi - transmission and semi - reflection is reduced.

[0124] According to one embodiment, additive manufacturing has a fused deposition modeling method for plastic parts of the sample holder, and the plastic parts include a thermoplastic, such as polylactic acid (PLA), or, for example, acrylonitrile butadiene styrene (ABS).

[0125] Advantageously, these polymers are commercially available and easy to process.

[0126] According to one embodiment, a method for analyzing a sample containing an analyte is proposed. The method comprises providing a sample holder for the sample according to any of the embodiments described above and further described below; placing the sample in the sample receiving chamber of the sample holder; directing a measurement light beam towards the sample receiving chamber; and collecting transmitted and / or semi-transmitted and semi-reflected light from the sample receiving chamber.

[0127] Advantageously, the method can be carried out such that the integrity parameters of the sample, such as sterility, volume, composition, color, viscosity, and / or shelf life, remain unchanged. Usually, the analyte is selected from biologically active substances, more typically pharmaceutically active substances, and / or their contaminants.

[0128] Furthermore, the analyte is usually dispersed or dissolved in a liquid or solid sample, and / or the sample usually contains a sterile medical / pharmaceutical preparation, for example for injection.

[0129] Preferably, the analyte is a compound containing chemical bonds (such as C-H, O-H, N-H bonds) that can interfere with an NIR light beam and / or chemical bonds (such as C-C, C=C, C-O bonds) that can function as Raman scatterers.

[0130] Furthermore, the analyte is usually dissolved in a liquid, and / or the sample usually contains a sterile medical / pharmaceutical solution, for example for injection.

[0131] According to one embodiment, the proposed method further comprises generating and analyzing the spectrum of the collected transmitted and / or semi-transmitted and semi-reflected light; and determining the parameters of the sample, for example identifying the presence of the analyte and / or the content of the analyte in the sample, the particle size, and the water content.

[0132] According to one embodiment, the proposed method described above further comprises the step of quantifying transmitted or semi-transmitted and semi-reflected light, the semi-transmitted and semi-reflected light including transmitted light emitted from an NIR spectrophotometer or a Raman spectrophotometer and reflected at the diffuser mirror of the sample receiving chamber.

[0133] According to one embodiment, a method for characterizing a sample for the identification, detection, or verification of conformance, semi-quantification, or quantification of an analyte is proposed, the method including measurement of semi-transmitted and semi-reflected and / or transmitted light by NIR spectrophotometry and / or Raman spectrophotometry using a sample holder according to any of the embodiments described above and further described below.

[0134] According to one embodiment of the proposed method, the analyte includes a cannabinoid selected from cannabidiol (CBD), tetrahydrocannabinol (THC), cannabidiolic acid (CBDA), tetrahydrocannabinolic acid (THCA), cannabinol (CBN), cannabigerol (CBG), cannabigerolic acid (CBGA), cannabichromevarin (CBCV), cannabichrome (CBC), cannabicyclol (CBL), cannabinol (CBE), cannabinodiol (CBND), cannabinotriol (CBTL), cannabidivarin (CBDV), and tetrahydrocannabivarin (THCV).

[0135] Advantageously, these analytes can usually be detected in medicinal cannabis preparations after their extraction by HPLC and / or mass spectrometry. However, HPLC and MS require special (and expensive) laboratory equipment and experts with high skills, while the proposed method is less expensive and at least not inferior in terms of sensitivity / reliability.

[0136] According to one embodiment, the cannabinoid is provided as a cannabis extract within a syringe, infusion bag, vial, bottle, or cuvette, soft or hard gelatin capsule, suppository, or cannabis flower part, and the syringe, infusion bag, vial, bottle, cuvette, soft or hard gelatin capsule, suppository, and cannabis flower part contain an oil, solution, or resin containing the cannabinoid.

[0137] Advantageously, these APIs according to the European Pharmacopoeia need to be monitored.

[0138] According to one embodiment, the analyte detected using the methods described so far contains caffeine.

[0139] Advantageously, the proposed method is simple, robust, highly reliable, and inexpensive compared to established methods.

[0140] According to one embodiment, the analyte is dissolved in a solution and / or the analyte is contained within a syringe, infusion bag, vial, bottle, cuvette, dragee, soft or hard gelatin capsule, tablet or film-coated tablet, or suppository.

[0141] Advantageously, these are typical dosage forms for many pharmaceutically active substances.

[0142] According to one embodiment, the syringe, infusion bag, vial, bottle, cuvette, dragee, soft or hard gelatin capsule, tablet or film-coated tablet, and suppository are surrounded by a secondary container.

[0143] In such a situation, the shape of the sample receiving chamber is adapted to the shape of the secondary container. On the other hand, usually, the secondary container is made of a flexible material that smoothly covers the primary container holding the sample.

[0144] Each of the embodiments described above can be combined with any other embodiment or embodiments unless the contrary is clearly indicated.

[0145] Regarding the figure, the drawing of FIG. 1 represents an embodiment 100 of a component-type cylindrical sample holder 10, which is configured to measure, for example, a sample S including dried herbs or flower buds and / or flower parts held in a transparent container C, for example. The sample holder 10 includes a diffusion mirror M. The container C is disposed on the measurement window W of a spectrophotometer. The container C with the sample S is covered by a bell-shaped sample holder 10. For example, a seam (not shown) is shaped so as to center the sample holder 10 that covers the container C directly above the measurement beam emitted by the light source LS of the spectrophotometer. The light TL transmitted through the sample S is reflected as reflected light RL by the diffusion mirror M and the reflective surface of the cylindrical sample holder 10, and finally reaches the corresponding detector, for example, a photoelectric element or an avalanche photodiode, as semi-transmissive and semi-reflective light in the measurement chamber of the spectrophotometer.

[0146] FIG. 2 shows another embodiment suitable for a smaller volume sample S, such as a liquid, solution, suspension, dispersion, or gel. This type of sample holder can also be used to compress, for example, dried herbs or flower buds of medicinal plant material in the container C. The container C is disposed inside a tubular element 11 having an inner diffusion mirror surface. The reflectivity of the inner surface may be different from that of the diffusion mirror M on the front surface of the plug-shaped element 12. Under the weight of the central plug-shaped element 12, the sample material S in the container C can be compressed. For this purpose, the plug-shaped element 12 is inserted into the container C containing the sample S. It includes the diffusion mirror M on its front surface. The plug-shaped element fits into the container C, and the container C is closely surrounded by the outer tube of the sample holder 110 having an inner reflective surface. Advantageously, the defined distance D between the wall of the container C located on the measurement window W and the diffusion mirror M can be set in such a self-adjusting manner.

[0147] FIG. 3 shows an embodiment 120 which is a modification of the previous embodiment 110. Advantageously, by combining the piston-shaped inner element 12, which is hollow, with the outer tube 11, material savings are possible.

[0148] The sample holder 140 according to the embodiment shown in FIG. 4 provides a sample receiving chamber SRC adapted to hold a sample S, such as individual soft or hard gelatin capsules, dragees, suppositories, tablets, or film-coated tablets. The sample receiving chamber SRC is formed by a first element providing an outer barrier 11 and a second element 12 comprising a diffusing mirror M. The outer contour of the second element 12 optimally fits the inner contour of the first element 11, or vice versa. Advantageously, the outer edge of the second element can be shaped to close the sample receiving chamber in a light-shielding manner on the side further away from the spectrophotometer. The first element 11 and the second element 12 together form a bell-shaped structure similar to the sample holder according to embodiment 100 described above. In the exemplary cross-section shown, the mirror M surrounds approximately 50% of the surface of the sample S. The mirror M can surround approximately 50% of the surface of the sample S in a plurality of parallel (virtual) cross-sections. In an embodiment that is rotationally symmetric with respect to the optical axis OA of the measurement beam, the mirror M can surround approximately 50% of the (total) surface of the sample S.

[0149] FIG. 5 shows a section used to generate the surface structure of a diffuser mirror. Typically, the section is created by the repetition of polygonal units / modules along an axis, for example the x-axis. In the figure shown, the polygon is a triangle having a height B, a base length C, and angles α, β, and γ. A copy of the first section (section 1) is offset by dimension A on the axis Y and further offset on the axis X so that the upper apex of the triangle of the first section (section 1) can share the same coordinates on the axis X as the lower apex of the triangle of the second section (section 2). The described process of adding another section is repeated until the required area of the diffuser mirror is covered. The required area of the diffuser mirror is defined by specific requirements, for example the geometry of the sample. FIG. 5 shows only one example of two periodically arranged repetitions and thus shows four sections shown. Other combinations of more sections having different values for A, B and / or C, and α, β and γ may be used to adapt the resulting waveform diffuser mirror to either the curvature of the container and / or sample, and / or the distance from the center of the sample receiving chamber and / or the central axis of the sample beam.

[0150] In other words, the reflective surface comprises a flat, curved, or more complex surface whose curvature and shape are adapted to the outer contour or shape of the sample. The main purpose of the above adaptation is to ensure reproducible and optimal measurement conditions and to ensure that the loss of intensity of the measurement light beam occurs mainly due to absorption by the sample. The reflective surface comprises a 3D pattern or 3D micropattern that provides a textured surface with depressions that function as diffusive mirrors on the surface. The 3D pattern is generated by lofting sections. The sections are created by repeating polygonal units / modules, more specifically triangular units / modules, more specifically isosceles triangular units / modules along an axis. This axis may be a straight line, curve, or polyline (in 2D or 3D), or a spline, or an irregular line. For example, a single triangle may have a base (C) and height (B) in the range of 0.01 to 2 mm, for example a base (C) of 2 mm and a height (B) of 1 mm, and angles α, β, and γ in the range of 1 to 175 degrees, for example α = 45°, β = 45°, and γ = 90°. This triangle is repeated along a row (axis X) over the longitude defined by the position and size of the required reflective area, and its total length is usually adapted to a specific sample or a part thereof. When the unit or module is repeated along this distance, a section is defined. A copy of this described section is offset, for example, by dimension A in the direction of axis Y, and then this copy is moved along axis X so that the upper apex of the triangle in section 1 can share the same coordinates on axis X with the lower apex of the triangle in section 2. This results in a 3D module that is an oblique triangular prism. The volume of such an oblique triangular prism is between 0.0005 mm 3 and 8 mm 3 more specifically between 0.005 mm 3 and 1 mm 3It may vary between. Thus, the surfaces resulting from the oblique triangular prism are arranged at angles between 89 and 1 degrees, more specifically between 60 and 20 degrees, towards the measurement light beam. If the triangular section is adapted, for example, to a semi-circular row, the triangular units / modules, and thus the resulting oblique triangular prisms and their angles are distorted.

[0151] In this context, the described geometries are implemented and stored within a suitable control program for a 3D printer used in normal 3D manufacturing processes. Thus, it is obvious to those skilled in the art of 3D manufacturing that precise descriptions of linear, inclined, diagonal, curved, and / or wavy, and at least partially repeating surface structures can be generated using the selected 3D printing technique.

[0152] Figure 6 shows some flat surface structures of a diffuser mirror that can be generated from the section shown in Figure 5. The various flat surface structures of the diffuser mirror are generated by lofting and parametrically fitting the surface in various procedures, and two points can be integrated in countless ways, thereby affecting the surface and / or pattern results. In particular, A in Figure 6 shows an embodiment including a smooth fit; B in Figure 6 shows an embodiment including a ruled fit; C in Figure 6 shows an embodiment including the normal for all sections; D in Figure 6 shows an example of the normal for the starting section; E in Figure 6 shows an example of the normal for the ending section; F in Figure 6 shows an example of the normal for the starting section and the normal for the ending section, and G in Figure 6 shows an example of an embodiment of a corrugated mirror surface including a draft angle. By repeating and mirroring this volume as a unit along the reflective surface, a 3D pattern with diffusing properties is generated. Thereby, between 500,000 and 10, more specifically between 50,000 and 25 per 1 cm 2 per cm 2 a density between is achieved.

[0153] Figure 7 shows the curved surface structure of the diffusing mirror M and the reflective surface obtained by the reflective coating R on the smooth portion of the mirror without such a surface structure. The shown curved surface structure of the diffusing mirror can be used in a reflective sample holder that holds a sample having a non-planar shape, such as a cylindrical shape. As shown, the curved waveform mirror surrounds at least a portion of the sample receiving chamber SRC.

[0154] FIG. 8 shows a cross-sectional view of a reflective sample holder 150 according to one embodiment for measuring a sample in a typical one-way syringe using a semi-transmissive semi-reflective technique. The reflective sample holder 150 shown consists of two elements, a body and a corrugated mirror M, and the corrugated mirror M is connected to a light guide channel G that includes a reflective coating R on its curved wall. The light guide channel has a circular cross-section at its bottom surface that is directed towards the light source of the spectrophotometer and centered with respect to the sample beam. In other words, the reflective sample holder according to embodiment 150 provides a sample receiving chamber SRC configured to hold a cylindrical sample S, such as a closed (e.g., capped) syringe holding a sterile medical caffeine solution, by the size and shape of its body. The sample receiving chamber SRC is formed by a first functional element that provides a reflective-coated surface R and a second functional element, namely a diffusive corrugated mirror M. The outer contour of the first functional element with the reflective coating optimally fits the inner contour of the second functional element and vice versa. Advantageously, the curved surfaces (the curvature) of the reflective coating R and the diffusive mirror M are adapted to the cylindrical shape of the sample S in order to minimize the loss of light intensity and enable maximum information to be obtained from the sample. In an exemplary embodiment, the mirror M surrounds approximately 50% of the outer surface of the inserted syringe and sample (not shown) respectively in the region of the light guide channel G and / or in at least one (usually multiple or even all) of the cross-sections that are parallel to the optical axis OA and cut the light guide channel G. In other embodiments, more or less than 50% of the outer surface of the inserted syringe and sample respectively is surrounded by the mirror M. As further shown in FIG. 8, the cross-section may be (at least substantially) parallel to the optical axis OA and (at least substantially) perpendicular to the symmetry axis SA of the sample receiving chamber SRC (and each sample when inserted into the sample receiving chamber SRC).

[0155] FIG. 9 shows a cross-section of a reflective sample holder according to another embodiment 160 for measuring a liquid contained within a syringe via a transmission mode. The reflective sample holder 160 shown consists of two elements and provides a sample receiving chamber SRC adapted to hold a cylindrical sample S, e.g., a syringe holding a medical caffeine solution. The sample receiving chamber SRC is formed by a first functional element for guiding an incident sample beam that provides a curved, reflectively coated surface R. Further, the sample receiving chamber of this embodiment includes a second functional element for guiding an exiting measurement beam, which also includes a reflectively coated surface, and this reflective coating R covers the flat and planar channel walls of the light guiding channel G. The exiting sample beam (above the body) "carries" or contains a signal characterized by an intensity that is primarily modulated by specific absorption and specific scattering of the incident measurement beam caused by, e.g., the constituents of the sample. Both reflective surfaces together represent a light guiding channel G that directs and guides a measurement light beam (sample beam) to pass through the sample from one side of the reflective sample holder and through the other side of the reflective sample holder. The outer contour of the second element optimally fits the inner contour of the first element, or vice versa. Advantageously, the reflective light guiding channel G is adapted to the cylindrical shape of the sample S in order to minimize light intensity losses and enable maximum information to be obtained from the sample S.

[0156] Figure 10 shows the NIR spectrum containing the measured values of a syringe holding a medical caffeine solution. These measured values were generated using the semi-transmissive semi-reflective technique. The blue line shows 10 measured values taken using the reflective sample holder 150 described herein, while the red line shows 10 measured values taken without a reflective sample holder using a generally available reflective gold mirror. This result demonstrates that it is possible to improve the overall quality of the measurement results and the overall reproducibility with the proposed reflective sample holder. The horizontal axis (x-axis) shows the wavelength represented by the wave number, and the y-axis (vertical axis) shows the corresponding signal intensity (absorbance).

[0157] Figure 11 shows the first derivative of a portion of the NIR spectrum shown in Figure 10, containing the measured values of a syringe holding a medical caffeine solution. These measured values were generated using the semi-transmissive semi-reflective technique. The blue line shows 10 measured values taken using the reflective sample holder 150 described herein, while the red line shows 10 measured values taken without a reflective sample holder using a generally available reflective gold mirror. This result demonstrates that it is possible to improve the overall quality of the measured values and the overall reproducibility with the reflective sample holder.

[0158] Figure 12 shows the NIR spectrum containing the measured values of a syringe holding a medical caffeine solution. These measured values were generated using the transmission technique. The blue line shows 10 measured values taken using the reflective sample holder 160 that enables the use of the transmission technique, while the red line shows 10 measured values taken without any additional tool. This result demonstrates that it is possible to improve the overall quality of the measurement results and the overall reproducibility with such a reflective sample holder.

[0159] Figure 13 shows the first derivative of a portion of the NIR spectrum shown in Figure 12, including the measured values of a syringe holding a medical caffeine solution. These measured values were generated using the transmission technique. The blue line shows 10 measured values taken using the reflection sample holder 160 that enables the use of the transmission technique, while the red line shows 10 measured values taken without any additional tools. This result demonstrates that such a reflection sample holder can improve the overall quality of the measurement results and increase the overall reproducibility. Figure 14 schematically shows some typical shapes such as soft gel capsules, suppositories, etc. that can be individually measured using the proposed sample holder.

[0160] Figure 14 schematically shows some typical shapes such as soft gel capsules, suppositories, pills, etc. that can be individually measured using the proposed sample holder, where the shape and curvature of the diffuser mirror are adapted to the shape and curvature of each sample. There, a) is an elliptical shape, b) is a spherical shape, c) is an oval shape, d) and g) are suppositories, e) is a tetrahedron, f) is a tub, h) is a star-like cushion, i.e., a "special shape", and i) is a twist-off soft gel capsule including, for example, a skin care product. The manufacturing method proposed herein for a sample holder with a diffuser mirror is flexible and adjustable to advantageously acquire digital data from a digital data set describing the sample. The digital data set can be used to control the machine for either the addition and / or removal treatment of the selected substrate (blank).

[0161] Briefly, there is proposed a sample holder (100, 110, 120, 140, 150) for spectrophotometric measurement of a sample (S) using a semi-transmissive semi-reflective technique, the sample holder comprising a sample receiving chamber (SRC) with a diffusive mirror (M), the curvature of the diffusive mirror (M) being adapted to the curvature of the surface of the sample (S) and / or to the curvature of the surface of a container (C) containing the sample (S). Further, there is proposed a sample holder (160) for spectrophotometric measurement of a sample (S) using a transmissive technique, the sample holder comprising a hollow light guiding channel (G), the inner wall of the hollow light guiding channel (G) being covered by a smooth reflective coating (R) and configured to at least partially surround a tubular portion of the sample (S) or of a container (C) containing the sample (S) along the circumferential direction of the tubular portion of the sample (S) or of the container (C).

[0162] Furthermore, a combination of manufacturing techniques for producing the sample holder is also disclosed, the combination comprising at least one of additive and subtractive manufacturing. Additive manufacturing involves performing 3D printing of at least a part of a wax model of the sample holder; and applying lost wax casting, which includes casting molten metal, molten metal alloy, and / or molten IR reflective polymer. Further, a method for analyzing a sample containing an analyte is proposed, the method comprising providing a sample holder for the sample; placing the sample in the sample receiving chamber (SRC) of the sample holder; directing a measurement light beam into the sample receiving chamber (SRC); and collecting transmitted and / or semi-transmissive semi-reflected light from the sample receiving chamber (SRC). Finally, a method for characterizing a sample for identification, qualification, semi-quantification, and quantification of an analyte is disclosed, the method comprising measurement of semi-transmissive semi-reflected and / or transmitted light by NIR spectrophotometry and / or Raman spectrophotometry using the sample holder.

[0163] The described embodiments have various applications in the detection of deteriorated products of pharmaceutical substances, their possible contaminants and / or admixtures, or substances biologically active for example, in the fields of medicine, pharmacy, veterinary medicine, or biochemistry, as well as in food, for example food additives, concentrates, etc., and in inexpensive goods, as a result of inappropriate storage conditions. For the purpose of demonstrating the feasibility of the proposed embodiments, several examples of the devices and methods used are provided and are shown by the accompanying drawings.

[0164] The invention has been described with reference to various exemplary embodiments and examples. These embodiments and examples are not intended to limit the scope of the invention as defined by the claims and their equivalents. As will be apparent to those skilled in the art, the embodiments described herein can be implemented in various ways without departing from the scope of the invention. The various features, aspects, and functions described in the embodiments may be combined with other embodiments.

[0165] Accordingly, a manufacturing technique for a sample holder is proposed, the sample holder being configured for spectrophotometric measurement of a sample using a semi-transmissive semi-reflective technique, the sample holder comprising a sample receiving chamber with a diffusing mirror, the curvature of the diffusing mirror being adapted to the curvature of the surface of the sample and / or to the curvature of the surface of the container containing the sample. Further, a sample holder for spectrophotometric measurement of a sample using a transmission technique is proposed, the sample holder comprising a hollow light guiding channel, the inner wall of the hollow light guiding channel being covered by a reflective coating, the diffusing mirror being configured to at least partially enclose and / or surround a sample, for example a soft gel capsule, or a part of the container containing the sample, along the convex part of the sample or the container. [Reference Signs] 10 Component-type cylindrical reflection sample holder 11 First element of the reflection sample holder 12 Second element of the reflection sample holder 100 Embodiment of the reflection sample holder 110 Reflective Sample Holder Embodiments 120 Reflective Sample Holder Embodiments 140 Reflective Sample Holder Embodiments 150 Reflective Sample Holder Embodiments 160 Reflective Sample Holder Embodiments C container D Thickness F. A film or coating (e.g. of a capsule) G Light guiding channel LS light source M Diffusion Mirror OA (from LS) measurement beam optical axis R Reflective Coating RL reflected light S Sample Axis of symmetry of SA, S and / or SRC SRC Sample Receiving Chamber TL transmitted light W Spectrophotometer measurement window

[0166] In the items attached below, the following reference symbols are used in accordance with the figures of priority application PCT / EP2021 / 069213, the disclosure of which is incorporated by reference in its entirety into this application: 1. Spectrophotometer (NIR or Raman spectrophotometer) 2 Liquids, e.g. biologically active substances, medicines, vaccines, food additives 3 Polymer containers (infusion bags, pumps or disposable plastic syringes, optionally packaged) 3a Tubular part of polymer container 3b Corners of polymer containers, especially infusion bags 4. Sterile packaging (usually made from polymer foil) 5 Optical elements, e.g. mirrors or light guides 6 Channels, e.g. light-guiding channels 66 Abutment portion and tongue portion of holder 13 7 Container holder 8 Lid 87 Edge, channel flange Opening of the light-shielding box 88 Light-shielding box 9 Measurement chamber extension part 10 Adapter 11 Adapter opening 11' Receptacle, holding member for the tubular part 13 Mirror fixing member 15 Measurement chamber 20 Bag orientation member 40 Outer contour of the bag orientation member 41 [Item] [Item 1] A measurement chamber extension part (10) for spectroscopic property evaluation of a liquid (2) in a polymer container (3) using a NIR spectrophotometer (1) or a Raman spectrophotometer (1), wherein the measurement chamber extension part (10) comprises: An adapter plate (11) having an adapter opening (11'); A container holder (7); and An optical element (5) selected from a mirror and a waveguide; Comprising The adapter (11) is configured to cover the measurement chamber (20) of the NIR spectrophotometer (1) or the Raman spectrophotometer (1) in a light-shielding manner, and the adapter opening (11') is arranged to surround the measurement window of the NIR spectrophotometer (1) or the Raman spectrophotometer (1), providing exposure of the liquid (2) to the measurement light beam emitted from the measurement chamber (20) of the NIR spectrophotometer (1) or the Raman spectrophotometer (1) through the measurement window; The container holder (7) is configured to be able to arrange the optical element (5) in proximity adjacent to the polymer container (3) containing the liquid (2), thereby providing lossless transmission or semi-transmission and semi-reflection of the measurement light beam from the optical element (5) to the detector of the NIR spectrophotometer (1) or the Raman spectrophotometer (1); and The container holder (7) has a clamp (13) configured to hold the tubular part (3a) of the polymer container (3) so as to enable reproducible measurement conditions. Measurement chamber extension part (10). [Item 2] The container holder (7) has an optical element support structure including a channel (6), and the width of the channel (6) is adapted to fit the width of the measurement window of the NIR spectrophotometer (1) or the Raman spectrophotometer (1). The measurement chamber extension part (10) according to Item 1. [Item 3] The optical element (5) has a mirror including a gold layer, or at least one optical fiber or waveguide. The measurement chamber extension part (10) according to Item 2. [Item 4] The optical element (5) has a mirror (5), and the container holder (7) has a receptacle (13) formed by the channel (6) together with the mirror (5). The measurement chamber extension part (10) according to Item 3. [Item 5] The surface (66) of the channel (6) is covered with a gold layer. The measurement chamber extension part (10) according to Item 4. [Item 6] The container holder (7) is optionally wrapped by a light-shielding box (9) including a lid (8), and the lid (8) is adapted to close the light-shielding box (9) in a light-shielding manner. The measurement chamber extension part (10) according to Item 4 or 5. [Item 7] The optical element (5) is fixed to the lid (8). The measurement chamber extension part (10) according to Item 6. [Item 8] The gold layer on the surface (66) of the channel (6) is integrated with the gold layer of the mirror (5), and the mirror (5) is incorporated into the channel (6). The measurement chamber extension part (10) according to Item 5. [Item 9] The mirror (5) is a diffused mirror (5). The measurement chamber extension part (10) according to any of the foregoing items. [Item 10] The gold layer includes a plurality of mirrors (55), each mirror (55) includes a flat polygonal surface, and the mirror (55) is arranged as the corrugated surface of the mirror (5). The measurement chamber extension (10) according to item 9. [Item 11] The surface of the mirror (5) includes a rough or smooth surface. The measurement chamber extension (10) according to item 10. [Item 12] The corrugated surface of the mirror (5) has a roughness in the range of 20 μm to 1000 μm. The measurement chamber extension (10) according to item 10 or 11. [Item 13] The optical element (5) is a waveguide. The measurement chamber extension (10) according to any one of items 1 to 3. [Item 14] On the measurement window of the spectrophotometer (1), a first waveguide for guiding measurement light from the light source of the spectrophotometer (1) to the liquid (2) in the polymer container (3) and to the optical element (5), that is, the second waveguide (5), is positioned. The second waveguide (5) is configured to guide the measurement light from the polymer container (3) to the photodetector of the spectrophotometer (1) after it passes through the layer of the liquid (2) in the polymer container (3). The measurement chamber extension (10) according to item 13. [Item 15] The polymer container is a disposable syringe (3). The measurement chamber extension (10) according to any one of the foregoing items. [Item 16] The light conductor (6) includes a channel (6). The ends of the channel (6) are shaped to be tongues (66) that form a receptacle (13) for fitting into and holding the tubular portion (3a) of the syringe (3) in an orientation perpendicular to the central axis of the channel (6). The surface of the tongue (66) substantially oriented towards the channel (6) includes a corrugated surface (55) including the mirror (5). The circular portion (3a) of the syringe (3) can be arranged in the receptacle within the optical path of the sample beam. The measurement chamber extension (10) according to item 15. [Item 17] The syringe (3) is the measurement chamber extension part (10) according to any one of Items 15 or 16, surrounded by a sterile package (4). [Item 18] The adapter opening (11') is the measurement chamber extension part (10) according to any one of Items 1 to 5, adapted to accommodate the corner (3b) of the infusion bag (3). [Item 19] Further comprising a bag orientation member (40), when the bag orientation member (40) is at least partially inserted into the adapter opening (11'), the outer contour (41) of the bag orientation member (40) is configured to fit the inner contour of the adapter opening (11') over most of the outer contour length, the measurement chamber extension part (10) according to Item 18. [Item 20] A corresponding pair of permanent magnets is arranged on or near the fitting edge of the adapter opening (11') and the bag orientation member (40), the measurement chamber extension part (10) according to Item 19. [Item 21] The thickness of the layer of the liquid (2) in the bag (3) is adjustable between 0.2 mm and 5.1 mm, preferably adjustable between 0.5 and 2.1 mm, the measurement chamber extension part (10) according to any one of Items 18 to 20. [Item 22] The mirror (5) is fixable by a mirror fixing member (15), the measurement chamber extension part (10) according to any one of Items 18 to 21. [Item 23] The mirror fixing member (15) and the bag orientation member (40) include at least one magnet of a pair of permanent magnets to stabilize the mirror in the channel (6), the channel (6) is dimensioned to surround the mirror (5), the measurement chamber extension part (10) according to Item 22. [Item 24] A method for analyzing a liquid (2) in a polymer container (3) selected from an infusion bag (3), a syringe (3), or a syringe (3) enclosed in a sterile package (4) by using a measurement chamber extension (10) according to any one of items 1 to 23, the method comprising: holding a circular portion (3a) of the polymer container (3) by a receptacle (13); positioning the optical element (5) of the measurement chamber extension (10) adjacent to the surface of the polymer container (3); directing a measurement light beam towards the optical element (5) and analyzing transmitted or semi-transmitted and semi-reflected light by using a spectrophotometer (1) selected from a NIR spectrophotometer (1) and a Raman spectrophotometer (1); comparing a signal generated by the transmitted or semi-transmitted and semi-reflected light with a data set stored in a database containing NIR spectra or Raman spectra of similar or identical samples; determining the identity of a solute dissolved or particles / liquid dispersed in the liquid (2) and / or detecting an admixture or contaminant in the liquid (2); or determining the amount of a solute dissolved or particles / volume of a liquid dispersed in the liquid (2) and / or detecting an admixture or contaminant in the liquid (2); and / or determining the physical properties (e.g., particle size, aggregation) of a solute dissolved in the liquid (2) or dispersed particles / volume of the liquid (2) and / or detecting an admixture or contaminant in the liquid (2) A method comprising the above steps. [Item 25] The method according to item 24, wherein the measurement light beam contains light within a wave number range of 4,000 cm -1 ~12,500 cm -1 The method according to item 24, wherein the measurement light beam contains light within a wave number range of 4,000 cm [Item 26] The method according to item 24 or 25, wherein in successive measurements, sample beams of various wavelengths are directed towards the optical element (5) and / or the measurement light beam is directed towards the optical element (5) at various angles. [Item 27] The method according to any one of items 26 to 28, wherein the database contains data sets belonging to various sample types, including the typical product range of the materials in the sterile packaging (4) of the polymer container and / or the syringe (3). [Item 28] The method according to item 27, wherein the software in the NIR spectrophotometer (1) or the Raman spectrophotometer (1), or in its control unit, is adapted to extract the corresponding spectrum belonging to the material including the sterile packaging (4) of the polymer container (3) or the syringe (3) from the measured NIR or Raman spectrum. [Item 29] A sample holder (100, 110, 120, 140, 150) for spectrophotometric measurement of a sample (S) using a semi-transmissive semi-reflective technique, the sample holder comprising a sample receiving chamber (SRC) having a diffusing mirror (M), the curvature of the diffusing mirror (M) being adapted to the curvature of the surface of the sample (S) and / or to the curvature of the surface of the container (C) containing the sample (S). [Item 30] The sample holder according to item 29, wherein the sample holder (100, 110, 120, 140, 150) comprises a hollow light guiding channel (G), the inner wall of the hollow light guiding channel (G) being covered by a smooth reflective coating (R), and configured to at least partially surround a part of the sample (S) or the container (C) containing the sample (S) along the circumferential direction of the tubular part of the sample (S) or the container (C). [Item 31] A sample holder (160) for spectrophotometric measurement of a sample (S) using a transmission technique, said sample holder comprising a hollow light guiding channel (G), the inner wall of said hollow light guiding channel (G) being covered by a smooth reflective coating (R), and said sample (S) or a part of a container (C) containing said sample (S) being configured to at least partially surround along the circumferential direction of the tubular portion of said sample (S) or said container (C). [Item 32] The shape of said sample receiving chamber (SRC) is configured to receive said container (C) containing said sample (S), said container (C) representing either the primary container of said sample or a single storage container, i.e., being the primary container or said container (C) representing a secondary container enclosing the primary container, and said sample (S) being disposed within said primary container, the sample holder according to any one of Items 29 to 31. [Item 33] Said container (C) includes at least one of plastic, paper, glass, metal, and fiber products, said paper and said fiber products may optionally be coated with a polymer, and said plastic is selected from a thermoformed polymer film, a polymer shrink film, and a plastic film bag, the sample holder according to any one of Items 29 to 32. [Item 34] Said sample receiving chamber (SRC) completely or at least surrounds along the circumferential direction of the tubular portion of said sample (S), the sample holder according to any one of Items 29 to 33. [Item 35] Said light guiding channel (G) is covered with a reflective coating (R), and said reflective coating (R) is reflective with respect to the light used for the measurement light beam, the sample holder according to any one of Items 30 to 34. [Item 36] The sample can be formed into a solid such as a crop, fruit, flower bud, flower part, plant extract, vegetable oil, or a powder or powder mixture that can be formed into tablets, and is selected from the following pharmaceutical dosage forms: tablets, coated tablets, suppositories, coated suppositories, hard gelatin capsules, soft gelatin capsules, candies, drops, ointments, creams, gels, lotions, dispersions, granules, solutions, injection solutions, infusions, and in particular, a liquid diet for enteral administration. The sample holder according to any one of items 29 to 35 is selected from these. [Item 37] The container (C) is selected from a syringe, infusion bag, vial, bottle, cuvette, blister, hard or soft gelatin capsule, film of a film-coated tablet, dragee, suppository, and film-coated suppository. The sample holder according to any one of items 29 to 36 is selected from these. [Item 38] At least a part of the sample receiving chamber (SRC) is included in one of a cylinder, tube, sphere, hemisphere, prolate spheroid, oblate spheroid, ellipsoid, ellipse, paraboloid, cube, cuboid, prism, pyramid, cone, frustum of a cone, hyperboloid, parabolic shape, helix, torus, parametric geometric shape, and differential geometric shape. The sample holder according to any one of items 29 to 37 is selected from these. [Item 39] The surface structure of the diffusion mirror (M) includes a plurality of geometric bodies or a part thereof. The geometric bodies are selected from a cylinder, tube, sphere, hemisphere, prolate spheroid, oblate spheroid, ellipsoid, ellipse, paraboloid, cube, cuboid, prism, pyramid, cone, frustum of a cone, hyperboloid, parabolic shape, helix, and torus. The sample holder according to any one of items 29 to 38 is selected from these. [Item 40] A combination of manufacturing techniques for producing the sample holder according to any one of items 29 to 39, wherein the combination of manufacturing techniques is carried out such that the diffusion mirror (M) is adapted to enclose and / or surround at least about 30% of the surface of the sample (S) and / or the surface of the container (C) in cross-section. The combination includes subtractive manufacturing and / or the combination includes additive manufacturing. The additive manufacturing usually Performing 3D printing of at least a part of the wax model of the sample holder; and Applying lost wax casting; including The lost wax casting includes casting molten metal, molten metal alloy, and / or molten IR reflective polymer, a combination of manufacturing techniques. [Item 41] A combination of manufacturing techniques for producing the sample holder according to any one of Items 29 to 40, the combination including subtractive manufacturing selected from turning, milling, boring, planing, drilling, reaming, electrical discharge machining, electro-erosion, etching, photolithography, and laser ablation, a combination of manufacturing techniques. [Item 42] The lost wax casting is Generating a casting mold for the part of the sample holder by embedding the 3D printed wax model; Covering the wax model with a mold-forming material to generate a mold, where the mold-forming material is selected from silica slurry, ceramic slip, and stucco; and drying the resulting green shell; Burnout and sintering the green shell to form the mold while the wax melts and leaves the shell and / or the mold; Casting by pouring molten metal or metal alloy into the mold; Removing the casting; Finishing the casting, finishing including at least one of grinding, polishing, plating, electroplating, and / or deposition of a reflective layer, particularly a gold layer, including, a combination of manufacturing techniques according to Item 41. [Item 43] The additive manufacturing includes a fused deposition modeling method for plastic parts of the sample holder, the plastic parts including thermoplastic plastics such as polylactic acid and acrylonitrile butadiene styrene, a combination of manufacturing techniques according to any one of Items 40 to 42. [Item 44] A method for analyzing a sample containing an analyte, the method comprising: providing a sample holder (100, 110, 120, 140, 150) for the sample as described in any one of Items 29 to 39; placing the sample in the sample receiving chamber (SRC) of the sample holder (100, 110, 120, 140, 150); directing a measurement light beam towards the sample receiving chamber (SRC); and collecting transmitted and / or semi-transmitted and semi-reflected light from the sample receiving chamber (SRC) A method comprising the steps of: [Item 45] generating and analyzing a spectrum of the collected transmitted and / or semi-transmitted and semi-reflected light; and determining a parameter of the sample, for example, identifying the presence of the analyte and / or the content of the analyte in the sample, the particle size, and the water content The method according to Item 44, further comprising the steps of: [Item 46] quantifying the transmitted or semi-transmitted and semi-reflected light, wherein the semi-transmitted and semi-reflected light includes transmitted light (TL) emitted from a NIR spectrophotometer or a Raman spectrophotometer reflected by a diffuser mirror (M) in the sample receiving chamber (SRC) The method according to any one of Items 44 or 45, further comprising the steps of: [Item 47] A method for characterizing a sample for identification, compliance, semi-quantification, and quantification of an analyte, the method comprising measuring semi-transmitted and semi-reflected and / or transmitted light by NIR spectrophotometry and / or Raman spectrophotometry using a sample holder as described in any one of Items 29 to 39 [Item 48] The method according to any one of items 44 to 47, wherein the analyte comprises a cannabinoid selected from cannabidiol (CBD), tetrahydrocannabinol (THC), cannabidiolic acid (CBDA), tetrahydrocannabinolic acid (THCA), cannabinol (CBN), cannabigerol (CBG), cannabigerolic acid (CBGA), cannabichromevarin (CBCV), cannabichromene (CBC), cannabinocyclol (CBL), cannabielsoin (CBE), cannabinodiol (CBND), cannabinotriol (CBTL), cannabidivarin (CBDV), and tetrahydrocannabivarin (THCV). [Item 49] The method according to item 48, wherein the cannabinoid is contained in a syringe, an infusion bag, a vial, a bottle, or a cuvette, a soft or hard gelatin capsule, a suppository, or a cannabis extract within a cannabis flower part, and the syringe, the infusion bag, the vial, the bottle, the cuvette, the soft or hard gelatin capsule, the suppository, and the cannabis flower part contain an oil, a solution, or a resin containing the cannabinoid. [Item 50] The method according to any one of items 44 to 49, wherein the analyte comprises caffeine. [Item 51] The method according to any one of items 44 to 50, wherein the analyte is dissolved in a solution and / or the analyte is contained in a syringe, an infusion bag, a vial, a bottle, a cuvette, a dragee, a soft or hard gelatin capsule, a tablet or a film-coated tablet, or a suppository. [Item 52] The method according to item 51, wherein the syringe, the infusion bag, the vial, the bottle, the cuvette, the dragee, the soft or hard gelatin capsule, the tablet or the film-coated tablet, and the suppository are surrounded by a secondary container.

Claims

1. A manufacturing technique for producing a sample holder configured for spectrophotometric measurement of a sample, using a semi-transmissive semi-reflective technique, wherein the sample holder includes a sample receiving chamber containing a diffusing mirror, and the curvature of the diffusing mirror is adapted to the curvature of the surface of the sample and / or the curvature of the surface of the container containing the sample, the manufacturing technique includes a subtractive manufacturing technique, Manufacturing technique.

2. A manufacturing technique for producing a sample holder configured for spectrophotometric measurement of a sample, using a semi-transmissive semi-reflective technique, wherein the manufacturing technique comprises the step of manufacturing the sample receiving chamber of the sample holder such that the sample receiving chamber includes a diffusing mirror, wherein the curvature of the diffusing mirror is adapted to the curvature of the surface of the sample and / or the curvature of the surface of the container containing the sample, and the diffusing mirror is adapted to enclose and / or surround at least about 30% of the surface of the sample and / or the surface of the container in cross-section. Manufacturing technique.

3. The manufacturing technique according to claim 2, wherein the diffusing mirror is adapted to enclose and / or surround at least about 50% of the surface of the sample and / or the surface of the container in cross-section, or even at least about 75% of the surface of the sample and / or the surface of the container.

4. The manufacturing technique according to claim 2 or 3, wherein the step of manufacturing the sample receiving chamber includes at least one of a subtractive manufacturing technique and an additive manufacturing technique.

5. The manufacturing technique according to claim 1, wherein the subtractive manufacturing technique is used to manufacture the diffusing mirror.

6. The manufacturing technique according to claim 1 or 5, wherein the subtractive manufacturing technique is selected from turning, milling, boring, facing, drilling, reaming, grinding, electrical discharge machining, electro-erosion, etching, photolithography, and laser ablation.

7. The manufacturing technique according to claim 1 or 5, wherein the manufacturing technique includes CNC machining.

8. The manufacturing technique according to claim 7, wherein the CNC machining includes at least one of turning, milling, boring, facing, drilling, and grinding.

9. The removal manufacturing technique according to claim 1 or 5, which is applicable to a material selected from wax, polymer, metal, alloy, and ceramic.

10. The manufacturing technique according to claim 1 or 5, further including an additive manufacturing technique.

11. The manufacturing technique includes: providing a blank; providing a first digital data set, the first digital data set describing the shape and / or curvature of the surface of the sample; generating a second digital data set from the first digital data set, the second digital data set at least describing the shape and / or curvature of the diffusion mirror of the sample holder including the diffusion mirror; applying the second digital data set to numerically control the movement and / or operation of a tool of a machine, wherein the tool forms at least a part of the sample holder from the blank. The manufacturing technique according to claim 1 or 2, comprising the above steps.

12. The manufacturing technique according to claim 11, wherein the part of the sample holder is the diffusion mirror.

13. The manufacturing technique according to claim 11, wherein the machine is a CNC machine.

14. The step of providing the first digital data set preferably includes scanning the sample to be measured digitally by a 3D laser scanning technique (*and obtaining a digital representation of the sample*). The manufacturing technique according to claim 11.

15. The manufacturing technique according to claim 11, wherein the second digital data set is based on or corresponds to a data set obtainable using slicing software.

16. The manufacturing technique according to claim 11, wherein the second digital data set is obtained from the first digital data set by scaling the radius of curvature of the curvature of the surface of the sample.

17. The manufacturing technique according to claim 1 or 2, further comprising a coating step for producing a reflective layer, wherein the coating step is particularly selected from electroplating, electroless plating, chemical vapor deposition, and physical vapor deposition of a gold layer.

18. A sample holder configured for spectrophotometric measurement of a sample using a semi-transmissive semi-reflective technique, the sample holder comprising a sample receiving chamber having a diffusing mirror, the curvature of the diffusing mirror being adapted to the curvature and / or shape of the surface of the sample and / or to the curvature of the surface of the container containing the sample, at least a part of the sample holder including the diffusing mirror is produced using the manufacturing technique according to claim 1 or 2, and / or the diffusing mirror is adapted in cross-section to enclose and / or surround at least 30% of the surface of the sample and / or the surface of the container, a sample holder.

19. the part of the sample holder including the diffusing mirror is the diffusing mirror, The sample holder according to claim 18.

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