Spectroscopic analysis of a sample

Abstract

Devices and methods for performing spectroscopic analysis of a sample, e.g., for performing Raman or other optical or spectroscopic analysis of a sample such as a pharmaceutical dosage form, including an oral solid dosage form such as a tablet or capsule, are described. Such a device can include a delivery optic arranged to direct probe light to a delivery region of a sample, a collection optic arranged to collect probe light scattered from a collection region of the sample, and a spectrometer having an entrance port arranged to receive the collected probe light from the collection optic at the entrance port of the spectrometer and to detect spectral features of the received probe light. In particular, the collection optic can include a Koehler integrating optic arranged to process the collected probe light so that the collected light from each point of the collection region is distributed over the entrance port of the spectrometer.

Description

[0001] This invention relates to apparatus and methods for performing Raman or other optical or spectroscopic analysis on samples such as pharmaceutical dosage forms, including oral solid dosage forms such as tablets or capsules. For example, Raman spectroscopy can be used in a transmission configuration to analyze such dosage forms or other samples. Background Technology

[0002] In various situations (such as sampling from a production line), it is desirable or necessary to test drug dosage forms to check whether they meet specific specifications. These specifications may define a narrow acceptable range of the absolute amount of one or more active pharmaceutical ingredients (APIs), as well as other aspects of the dosage form, such as shape, size, and the content and properties of other chemical components.

[0003] One way to determine these contents and chemical properties is to grind each sample dosage form into a powder, dissolve it in a solvent, and introduce it into a liquid chromatograph, mass spectrometer, or similar instrument. However, this process can be slow and difficult to automate effectively when a large number of dosage forms need to be tested individually. Accurately tracking the characteristics of each dosage form sample through this analytical process is challenging, and the physical properties and identifying markers of the original dosage form can be lost during the process.

[0004] For example, PCT / SE96 / 01637 and WO 2007 / 113566 describe spectroscopic tests for drug dosage forms used in quantitative analysis. Dosage forms can be in the form of tablets, capsules, and other formulations. However, performing such spectroscopic tests on multiple similar samples in a consistent manner can be challenging, as even seemingly identical samples can sometimes yield sufficiently different and noteworthy results.

[0005] The present invention aims to address the problems and limitations of the prior art. Summary of the Invention

[0006] Typical spectroscopic systems (such as Raman systems) use an imaging lens system to couple light from the sample to the spectrometer input, either directly to the spectrometer port or via imaging to the input surface of the fiber bundle. This means that the light distribution at the spectrometer input contains spatial information related to the sample morphology. However, in many cases, it may be desirable to sample the sample volume or bulk, or otherwise perform spectral analysis that is insensitive to the precise location, orientation, or motion of the sample, and thus also provide improved spectral consistency among multiple similar samples.

[0007] Spectral changes caused by variations in the sample's position, orientation, or motion can manifest as intensity fluctuations or peak shifts. In backscattering configurations, intensity fluctuations occur due to variations in the sample surface angle and illumination relative to the collecting optics, as well as variations in the location of surface features. For transmission configurations, even small variations in sample orientation and position can result in different optical path lengths and geometries through the sample, especially if the sample has varying thickness or contains surface or subsurface features.

[0008] The position of spectral peaks may shift because intensity fluctuations can cause differences in the angle input of the light entering the spectrometer. Spectrometers where the slit is directly illuminated by light from the sample are likely most sensitive to this effect, but systems that transmit light to the slit via optical fiber are not immune, especially when the numerical aperture of the fiber is larger than that of the spectrometer.

[0009] Therefore, the present invention addresses the problem of angular and spatial variations of light from a sample introduced into a spectrometer. If the sample is a pharmaceutical dosage form, such as multiple similar or substantially identical tablets or capsules, which typically include embossed or recessed patterns or other surface markings and geometry, minute variations in the position or orientation of these dosage forms can affect the distribution of light entering the spectrometer, leading to inconsistencies in spectral measurements and thus inconsistencies in property determinations among multiple such samples.

[0010] To this end, the present invention provides an apparatus for sample spectral analysis comprising Koehler integrating optics to propagate light collected from the sample in a uniform manner independent of the sample's geometry. This is achieved by imaging an intermediate plane and projecting that distribution. This ensures that spatial information from the sample surface is not coupled into the spectrometer input. This does not necessarily eliminate far-field variance, but this variance can be addressed using a "fly-eye" microlens array configuration of the Koehler optics, where a pair of matched microlens arrays are used for secondary sampling of the intermediate aperture. This ensures that all spatial and angular information is averaged to provide a very uniform near-field and far-field light distribution.

[0011] This means that light from each location on the sample surface is distributed across all the fibers of the fiber bundle that carries the light to the spectrometer, or across the entire input light entering the spectrometer, rather than across a single fiber or a portion of the spectrometer port corresponding to a location or region on the sample surface. Even when using only a single fiber instead of a bundle of fibers to carry the light to the spectrometer, the use of this invention provides a better distribution of light entering the single fiber from the sample surface.

[0012] The positional offset of the sample and any surface features relative to the optics used to collect light will thus greatly reduce their impact on the structure of the light entering the spectrometer. Furthermore, all fiber optic and / or spectrometer port portions will carry the same spectral information, facilitating more advanced analytical modes of the spectral data detected at the spectrometer.

[0013] Therefore, various aspects of the present invention provide methods and apparatus for performing spectral analysis on samples, wherein a collection optics collects probe light from the sample, and a spectrometer receives the collected probe light from the collection optics, wherein the collection optics includes a Koehler integrator or integrator optics that processes the collected probe light before it is transmitted to the spectrometer. In particular, the Koehler integrator optics are operable such that light collected from each point in the collection region is distributed over most or all of the spatial range of light received at the spectrometer.

[0014] However, other different optical arrangements can be used alternatively to process the light collected from the sample in order to reduce or remove spatial sample image information from it before the collected light is input to the spectrometer. For example, optics such as compound hyperbolic concentrators or non-imaging concentrator lenses can be used alternatively to process the collected light in a manner that does not preserve spatial information of the sample at the input plane or port of the spectrometer.

[0015] More specifically, various aspects of the present invention provide an apparatus for performing spectral analysis on a sample, the apparatus comprising: a transfer optics arranged to guide probe light to a transfer region of the sample; a collection optics arranged to collect probe light scattered from a collection region of the sample; and a spectrometer having an inlet port arranged to receive the collected probe light from the collection optics at the inlet port of the spectrometer and to detect the spectral characteristics of the received probe light, wherein the collection optics includes a Koehler integrating optics, or other non-imaging optics arranged to have a similar effect. The Koehler integrating optics and other non-imaging optics can be described as being arranged to process the collected probe light such that the collected light from each point of the collection region is distributed at the inlet port of the spectrometer.

[0016] The sample can typically be a solid sample, such that the transfer region and the collection region are areas on one or more surfaces of the sample. Different geometries and locations of the transfer region and the collection region can be used, for example, in backscatterer and transmission geometries to enable optical analysis of the sample with different geometries.

[0017] The device may further include one or more suitable light sources to generate the probe light for guiding at the sample, such as one or more infrared lasers. The device may further include an analyzer arranged to determine one or more properties of the sample from detected spectral features, such as the presence or measured content of a specific chemical substance inside or on the surface of the sample.

[0018] The device can realize the Raman spectrum of the sample, such that the detected spectral features are or include Raman spectral features from which the properties of the sample can be determined, such as the amplitude of one or more Raman spectral peaks.

[0019] The collecting optics may include a bundle of two or more optical fibers (or a single optical fiber in some embodiments), the bundle having: an incident surface arranged to receive probe light collected after processing by a Koehler integrating optics; and an exit surface arranged to deliver the collected probe light to a port of the spectrometer, which may typically be a slit of the spectrometer.

[0020] While in some geometries used for sample analysis, the transfer and collection regions can coincide or overlap to achieve a backscattering geometry, in other geometries, the collection region can be spaced apart from the transfer region. In particular, the collection region can be on the side of the sample opposite to the transfer region, such that in a transmission geometry, light is collected from the collection geometry after being scattered forward within the sample.

[0021] Typically, a Koehler integrating optics may include a collector arranged to receive collected light from a collection region of a sample, and a condenser arranged to receive the collected light from the collector. Each collector and condenser may include one or more simple or composite lenses, and these lenses may be spherical or aspherical as needed.

[0022] The Koehler integrating optics may thus include or define an intermediate plane at or near the collector and an output plane, the collector being arranged to form an image of the collection region of the sample at or near the condenser, and the condenser being arranged to form an image of the intermediate plane at the output plane.

[0023] In this context, the term "proximal" can mean, for example, that the image of the collecting region is formed within ±10% of the distance from the optical center or optical element of the collector to the optical center or optical element of the condenser, and / or that the intermediate plane lies within ±10% of the distance from the optical center or optical element of the condenser to the optical center or optical element of the collector. Similar interpretations of "proximal" can be used in other cases. The term "proximal" is used because precise positioning of elements, images, etc., may be desirable for optimal functioning of a Koehler integrating optics, but may not be strictly necessary to meet required performance in order to still function as a Koehler integrating optics, as understood by those skilled in the art.

[0024] The collecting optics may include an optical fiber, or more generally a bundle of optical fibers, having: an incident surface arranged to receive the probe light collected after processing by the Koehler integrating optics; and an exit surface arranged to transmit the collected probe light to a port of the spectrometer. The output plane of the Koehler integrating optics can then be located at or near the incident surface.

[0025] The collecting optics may include one or more sets of collimating lenses and one or more spectral filters disposed within each set of collimating lenses. Each set of collimating lenses is arranged such that the collected light is collimated as it passes through one or more spectral filters disposed within the set. This collimation allows for improved operation of the spectral filters, particularly if the spectral properties of the spectral filters depend on the angle of incidence, such as when using multilayer dielectric (interference) filters. In this regard, the collimation provided by the collimating lenses may only be moderate, for example, 90% of the collected light may be within 10 or 20 degrees of the optical axis of the collecting optics or Koehler integrating optics.

[0026] A set of collimating lenses may be lenses of the collector, and one or more of the spectral filters may thus be included within the collector or may provide the collector.

[0027] Alternatively or concurrently, a set of the collimating lenses may be included in or provided in an output transponder arranged to transpond the image from the output plane of the condenser, and one or more of the spectral filters may then be included in the output transponder.

[0028] Alternatively or concurrently, a set of said collimating lenses may be included in or define a sample transponder arranged to form a transponded virtual image of the collection region for imaging by the collector, and one or more of said spectral filters may be included within the sample transponder. A sample aperture may be provided between the sample transponder and the collector, the sample transponder being arranged to form a transponded virtual image of the collection region at the sample aperture.

[0029] As described above, the detected spectral features can be Raman spectral features, which are defined based on the wavenumber shift of one or more probe wavelengths of the probe light directed to the sample transfer region. The one or more spectral filters may then include spectral filters arranged to block light of the original probe wavelengths but allow light of the Raman spectral features to pass through.

[0030] The device may further include a sample aperture and a sample transponder, the sample transponder being arranged to form a transponded virtual image of a collection area at the sample aperture for imaging by the collector.

[0031] The device may further include a condenser aperture at or near the condenser, such that the condenser aperture limits the extent of the virtual image of the collection area formed by the collector at or near the condenser.

[0032] In some arrangements, the collector may include a collector microlens array, and the condenser may include a corresponding or matched condenser microlens array. These microlens arrays may be confocal, meaning they may be located at each other's focal length. The microlens arrays can thus be arranged to double-sample the apertures of the collector and condenser. These double-samples are then superimposed at the output plane, further reducing the spatial image information of the collection region in the processed collected light.

[0033] Various different samples can be analyzed using the described equipment and methods, but in some embodiments, the sample can be a pharmaceutical dosage form, such as one or more of the following: tablets; coated tablets; capsules; and pellets; and can include one or more of the following: surface markings; grooves; embossing; multiple surface areas, each with a different color; and imprints.

[0034] The described transmission geometry can be used in particular to determine the properties of the body of such drug dosage forms, where the use of Koehler integrating optics in the collector minimizes spectral artifacts caused by minute differences in the arrangement or orientation of each of several similar dosage forms, thereby improving analytical consistency across multiple dosage forms.

[0035] The present invention also provides methods corresponding to the implementation and operation of the described device, such as a method for performing spectral analysis on a sample, the method comprising: directing probe light to a transfer region of the sample; collecting the probe light from a collection region of the sample; processing the collected probe light such that the collected light from each point of the collection region is distributed across the entire inlet port of the spectrometer; and transferring the processed collected probe light to the inlet port of the spectrometer.

[0036] For example, processing the collected probe light may include applying Koehler integration or other de-imaging processing to the collected probe light.

[0037] The method typically includes a spectrometer that detects one or more spectral properties of collected and processed light and determines one or more properties of the sample based on the detected spectral properties. In particular, the one or more spectral properties are Raman spectral properties.

[0038] The sample may be a drug dosage form. Transmission geometry can be used to help determine the nature of the bulk of the dosage form, wherein the delivery region is on the side of the sample opposite to the collection region, or at least spaced apart from the collection region. Attached Figure Description

[0039] Embodiments of the invention will now be described by way of example only with reference to the accompanying drawings, wherein:

[0040] Figure 1 An apparatus for performing spectral analysis on samples such as pharmaceutical dosage forms arranged in a transmission geometry is schematically shown.

[0041] Figure 2 It shows something similar to Figure 1 The device, but used a reflective geometry for the probe light at the sample;

[0042] Figure 3 It shows that it can be achieved Figure 1 and Figure 2 One method of using Koehler integrating optics;

[0043] Figure 4 and Figure 3 Similarly, the collector includes a collimating lens and a spectral filter;

[0044] Figure 5 and Figure 3 Similarly, an output transponder for including spectral filters is added after the Koehler integrating optics;

[0045] Figure 6 and Figure 3Similarly, a sample transponder was added before the Koehler integrating optics;

[0046] Figure 7 This demonstrates how Koehler integrating optics can be implemented using a small lens array;

[0047] Figure 8 This is an intensity diagram of each fiber in the fiber bundle under slight sample movement, with and without the use of Koehler integrating optics; and

[0048] Figure 9 A method according to the present invention is shown. Detailed Implementation

[0049] refer to Figure 1 The diagram schematically illustrates an apparatus 10 for performing spectral analysis on a sample 12, such as a pharmaceutical dosage form, which may be, for example, an oral solid dosage form (such as a tablet or capsule), but other types of dosage forms or even other kinds of objects can be analyzed using the apparatus and techniques described herein.

[0050] The apparatus 10 is arranged and operated to provide improved consistency for spectral or other optical analyses on multiple similar samples 12, such as a batch of substantially identical drug dosage forms. Such a batch of dosage forms may typically be identical or very similar on the surface (e.g., in terms of shape, size, and composition), but may still contain defects and / or variations, particularly in terms of internal chemical content and composition. Detecting such defects and variations may be important as part of the manufacturing process or other testing scenarios.

[0051] Tablets are manufactured in various shapes, sizes, and colors. Some tablets can have multiple different colors. Tablet shapes include cylindrical or elliptical prisms, often with beveled edges, spherical, oval, rhomboid, etc. Tablets are often embossed or engraved with markings such as alphanumeric codes and other symbols, seams to facilitate splitting into multiple parts, and other surface features. Some tablets carry printed surface markings, including alphanumeric codes and other symbols. Tablets are manufactured in coated and uncoated forms; in the coated form, the surface layer contains a different component than the underlying tablet core.

[0052] Drug capsules (of which gel capsules are a special form) typically consist of a sleeve containing drug powder or sometimes a gel or fluid. The typical shape of a capsule is a cylinder with rounded ends, but other geometries, such as a flattened cylinder, are sometimes used. The sleeve is usually formed by joining two opposing end segments, which are often different colors. Capsules are typically marked with surface markings (such as alphanumeric codes and other symbols).

[0053] The inventors have discovered that various physical characteristics of dosage forms (such as those described above) can affect the consistency of optical analysis results among many dosage forms of the same type or batch, even if these dosage forms appear identical. It has been determined that consistency may be reduced, for example, if such dosage forms are presented for optical analysis with different orientations, rotational states, or different positions of these characteristics relative to the optical analysis instrument. A very small number of dosage forms (which may require optical analysis) are essentially devoid of any such characteristics or asymmetries.

[0054] Figure 1 The device shown can be used as part of an instrument that provides automated and continuous optical analysis of multiple samples (such as multiple dosage forms with identical or similar surfaces), thereby providing improved consistency in optical analysis. A typical application area could be for monitoring the chemical compositional properties of dosage forms sampled from a production line or other manufacturing process. Determining the properties of a dosage form can include measurements or concentrations or quantities of one or more active ingredients or other components, as well as measurements or concentrations or quantities of one or more polymorphic forms, hydrated forms, solvated forms, salt forms, and crystallinity of such active ingredients or components. The presence or concentration of impurities can be detected similarly.

[0055] Figure 1 The apparatus shown is specifically configured to perform Raman spectroscopy analysis on sample 12 (such as a pharmaceutical dosage form), but can also, or alternatively, perform other types of spectral analysis or more general optical analysis. Figure 1 The operating mode of the device shown is one of the transmission Raman spectroscopy methods, in which probe light is transmitted to a transmission region 13 on a first surface 14 of a sample 12 via a transmission optics 16, and a collection optics 20 collects the probe light component that has been scattered forward through the sample 12 from a collection region 17 on a second surface 18 of the sample, for detecting the Raman scattering component in the collected light. Such transmission Raman techniques are described, for example, in WO2007 / 113566, the contents of which are incorporated herein by reference for all purposes and more specifically for describing the ways in which transmission Raman techniques can be implemented.

[0056] Typically, in a transmission configuration, the second surface 18 can be spaced apart from the first surface 14 such that the Raman scattering component of the probe light carried by forward scattering is brought to the second surface for collection and detection, thereby analyzing the sample in either transmission or forward scattering geometry. While different arrangements are possible, Figure 1 In this example, the second surface 18 is located on the side of the sample opposite to the first surface 14. This example is shown as follows. Figure 1The tablet dosage form sample 12' shown in the unfolded view has a first surface 14, which is the first large plane of the tablet dosage form 12', and a second surface 18, which is the second large plane of the tablet dosage form 12', opposite to the first surface 14. For some dosage forms, and more generally for tablet forms, each of the first and second surfaces may be substantially parallel, typically circular, and spaced apart from each other by sidewalls, such that the dosage form typically has a rectangular cross-section, such as... Figure 1 Seen in the main part.

[0057] The shape and size of the transmission area 13 and the collection area 17 can be selected according to needs and design. Typically, in transmission geometry arrangements (such as...) Figure 1 In the transmission geometry arrangement, the transmission area can be a circular or elliptical region with a diameter of approximately 1 mm to 10 mm, and the collection area can be a circular or elliptical region of similar size. The transmission area does not have to be a continuous region, but can consist of multiple separate regions, and the same applies to the collection area.

[0058] Figure 1 The device includes a laser source 22 arranged to generate a probe beam (typically an infrared laser), and a transmission optics 16 that guides the probe beam to the sample 12. A collection optics 20 is arranged to receive the probe beam after forward scattering (including Raman scattering) within the sample 12 and transmits the collected probe beam to a spectrometer 26.

[0059] Typically, spectrometer 26 can be a dispersive spectrometer, such as a Kaiser Optical Technology holographic spectrometer. A collecting optics directs the collected probe light to an inlet port 28 of spectrometer 26. Inlet port 28 is typically a slit, its width chosen to provide a suitable trade-off between light focusing and spectral resolution, and its length related to the size of imaging element 30. However, other types of ports, such as binary-coded ports, can be used.

[0060] The spectral characteristics S of the collected probe light, and especially Raman spectral characteristics, can then be detected by a CCD or other imaging components 30 forming part of the spectrometer 26. The detected Raman spectral characteristics S (using...) Figure 1 (As shown in the small figure) can then be transmitted from spectrometer 26 to analyzer 50 in the form of electronic data for further processing and use. Raman spectral features 31 and / or additional data derived from the spectral features can then be transmitted to other entities (such as locally connected personal computers 52) via one or more data networks, or stored on a data carrier for future use.

[0061] For ease of construction and flexibility, the collecting optics typically include a bundle of optical fibers 32, or sometimes only a single optical fiber, which carries the collected light to the spectrometer 26, typically to the inlet port 28. Figure 1 In the diagram, the fiber bundle is also shown as bundle 32' in an extended view, where it can be seen that the fiber bundle can present an incident surface 34 and an exit surface 36. In the incident surface, the ends of the individual fibers are gathered in a generally circular encapsulation, such as a similar hexagonal tight package, and in the exit surface, the ends of the individual fibers are distributed along the elongated encapsulation, such as in a line. In this way, light collected from the second surface of formulation 12 can be easily projected onto the incident surface 34 of the fiber bundle 32 using other parts of the collecting optics, and can be easily guided into the elongated entry port or slit 28 of the spectrometer 26 through the exit surface 36.

[0062] Typically, the laser source 22 can operate in the near-infrared range (e.g., about 700 nm to 1000 nm), as a continuous wave or pulsed laser source. A suitable average optical output power delivered to the sample 12 can be about 50 to 1200 mW, and a suitable spot diameter for the probe beam at the sample 12 can be in the range of about 1 to 10 mm. Particularly small spot sizes can be avoided due to the risk of heat or optical damage to the sample during testing.

[0063] In implementing Raman spectroscopy, the collecting optics 20 are typically designed to very effectively suppress the wavelength band (i.e., the fundamental wavelength) of the probe light emitted by the laser source 22. The Raman scattering cross-section is very small, so without such suppression, the fundamental wavelength is likely to adversely affect the accurate detection of Raman spectral features, even if these features are tens of nanometers or more away from the laser band. This suppression can be achieved by using one or more optical filters (such as holographic notches or low-pass filters) in the collecting optics 20 to suppress laser band light that is elastically scattered away from, through, or around the sample under test, as discussed in more detail below.

[0064] During optical analysis, the sample 12 can be supported or held in various ways by the support 40. For example, the support 40 can be provided by a frame, within which the sample is placed or held by the gripper of a robotic manipulator or otherwise. When detecting Raman spectral features 33, the suppression of laser-band light in the collecting optics 20 reduces the need to prevent stray probe light from being reflected or scattered around the sample 12 and entering the collecting optics, which is often necessary when using infrared absorption spectroscopy and some other spectroscopic techniques. As a result, in many implementations, the sample 12 can be suspended by the support 40 without the particular need for an optical seal around the sample side between the transfer optics 26 and the collecting optics 30 to prevent such stray light.

[0065] Analyzer 50 may be arranged to determine one or more properties P of sample 12, such as the aforementioned chemical properties, based on Raman spectral features 31 provided by spectrometer 26. For example, analyzer 34 may be arranged to detect, for example, the amplitude of a particular Raman spectral peak and other features indicating a particular chemical component expected or sought in the sample, a broader spectral match with the spectra or multiple spectral features of these components, for example, by referring to one or more databases defining the expected spectra and / or specific spectral features of these components.

[0066] The spectral data S and / or determined properties P of the sample under test can be used in various ways, such as being stored locally and / or remotely, transmitted over a network, further analyzed, or used to control processes such as the manufacturing process used to create the sample under test. Figure 1 In this context, a local personal computer 52 is shown to receive a determined property P and can, for example, provide an output of an aspect of the determined property to a person monitoring device 10, such as in the form of a display of the deviation of the determined property from the expected value, an auditory or visual alarm, to draw the person's attention to a sufficiently significant deviation, etc.

[0067] exist Figure 1 In the transmission arrangement, the Raman spectral features S output by the spectrometer 26 can be detected as the overall average of the sample or other representative datasets, at least to some extent, the collected light embodies the entire sample. In fact, Figure 1 The transmission Raman technique demonstrated is particularly adept at sampling the bulk of a sample (such as a dosage form), where the collected light carries Raman spectral characteristics derived from the large volume within the sample. Thus, the determined property P can be a property of the dosage form or other sample as a whole, and remains comparable between the tested dosage forms or other samples.

[0068] However, the inventors have found that such consistency is difficult to achieve the high accuracy required in fields such as manufacturing and testing of samples, such as pharmaceutical dosage forms. It appears that various asymmetries and features of dosage forms or other test samples (such as overall shape, surface, color features, grooves and embossing, and imprints) combined with minute variations in the positioning of the sample to be analyzed (including potential minute deviations in the position or geometry of the surface region of the sample from which the probe light is guided and from which scattered light is collected for analysis) can lead to relevant intensity deviations at the position of the entry port 28 across the spectrometer 26, both as a function of position, for example, along the length of the spectrometer slit, and as a function of angular distribution.

[0069] Therefore, the detected intensity of Raman spectral features (such as peaks) will vary slightly depending on the precise positioning and alignment of the analyte. Furthermore, since actual spectrometers also exhibit slight shifts in the apparent detection wavelength and detected intensity based on the spatial and angular distribution of light collected at the inlet port or slit, the detected spectral position of Raman spectral features (such as peaks) can also vary slightly depending on the precise positioning and alignment of the analyte.

[0070] If the collected light is directly projected onto the spectrometer inlet port 28, these deviations in the intensity and spectral position of the spectral feature S output by the spectrometer tend to be more pronounced, but even when the collected light passes through... Figure 1 These deviations are still large enough to be of concern when the optical fiber or fiber bundle 32 is transmitted to the inlet port 28, especially if the numerical aperture of the optical fiber or bundle is higher than the numerical aperture of the spectrometer 26.

[0071] Figure 1 The collecting optics 20 therefore includes de-imaging optics, or more specifically, Koehler integrating optics 100, which operate to remove image structures from the light collected from the sample 12 as it travels to the entrance port 28 of the spectrometer 26. By removing such image structures, changes in the position or orientation of the sample relative to the collecting optics have a smaller effect on the distribution of light across the spectrometer port. This process can be described in various ways, for example, as processing the collected light such that the light collected from each point in the collecting region is distributed across most or all of the entrance ports of the spectrometer. In this respect, each point in the collecting region can ideally contribute equally to each portion of the light entering the entrance port, but of course, such a complete level of de-imaging is not necessary to provide a useful level of image information removal.

[0072] Using Koehler integrating optics to achieve this effect also maintains a reasonable and efficient use of the available collected light, although the number of optical elements in the collecting optics may need to be increased. This can be important for many reasons. In spectroscopic applications, and especially in such applications using Raman spectroscopy with low collision cross-sections, efficient use of the collected light reduces exposure and integration times (which can often take many seconds or even many minutes), lowers probe power (making it easier or cheaper to achieve the desired power levels, stability, etc., and reducing the possibility of optical / thermal damage to the sample), and makes it easier to achieve the desired spectral resolution and detector sensitivity.

[0073] Figure 2 It demonstrates that it can be implemented more generally. Figure 1 Different approaches in various aspects. Figure 1 And the details mentioned above can be included as needed. Figure 2 In the arrangement. Figure 2 The laser source 22 is not depicted in the image. Irradiation of sample 12 can be achieved using methods such as... Figure 1 The laser source 22 depicted uses a transfer optics; however, alternatively, the light source 22 can be provided by any light source suitable for the spectroscopic determination to be performed, and is not necessarily a laser source. For example, an LED or other broadband light source can be used with appropriate filters to achieve the spectral narrowing required for the implemented spectroscopic technique. In some cases, the use of ambient light, sunlight, or other sources may be desired or suitable. If the light source is able to form a suitable beam, or if a specific beam is not required to irradiate the sample, a separate or specific transfer optics may not be necessary.

[0074] Although Figure 1 The sample is held in place by a support 40. Figure 2 This type of support is not depicted, but any kind of support, carrier, holder, manipulator, or other arrangement suitable for managing and holding the sample in place may be used as needed. In some embodiments, sample 12 may be all or part of an object to be tested in situ, such as an object in a warehouse or on a conveyor belt, or a surface in a building, or an object on a table.

[0075] Although Figure 1 A transmission geometry is used to guide the probe light to a transmission region 13 spaced apart from or opposite the collection region 17, such that the probe light is forward-scattered through the sample body before exiting the collection region 18 for collection. Figure 2 A specific geometry is not shown. Although shapes such as... can be used... Figure 1 While transmission geometries may be used, the sample can also be illuminated by probe light in various other ways, such as by providing probe light directly onto some or all of the collection area, from which collection optics collect the probe light for spectral analysis in a reflective or backscattering geometry. In this case, the collection area and the transmission area are described as coincident or overlapping. Probe light can be transmitted to the sample along or near the collection beam path, or along some other path (e.g., an off-axis path relative to the collection path), for example, by using partial or other mirrors. Other geometries may include transmitting probe light at some intermediate angle between a transmission geometry and a backscattering geometry, such as tilted or perpendicular to the collection path, or directed to the sidewalls or sides of the sample.

[0076] like Figure 1As already depicted, the collecting optics 20 are arranged to collect the probe light scattered from the collecting region 17 of the sample. From the perspective of the collecting optics, the collecting region can be the entire visible surface of the sample, or a smaller portion of the visible surface, such as... Figure 2 As seen in the image. Furthermore, the collection area can be a single continuous region, or it can comprise two or more separate regions. While a generally circular collection area may be consistent with the use of geometric optics in the collection optics, the collection area can have a variety of other shapes or forms. The sample can be positioned very close to the collection optics, or at a greater distance; in the case of a greater distance, suitable telescopic optics may be incorporated within the collection optics.

[0077] Spectrometer 26 is arranged to receive the collected probe light from the collecting optics at the spectrometer inlet port 28 and to detect the spectral characteristics of the received probe light. Similarly... Figure 1 As already described in, such as Figure 2 The collection optics shown include a Koehler integrating optics 100 (or other de-imaging optics), which are arranged to process the collected probe light for transmission to the spectrometer's inlet port, as described elsewhere in this document. (See also: Regarding...) Figure 1 The optical fiber or fiber bundle 32 may be used to transmit the processed light from the Koehler integrating optics to the spectrometer, or other optical arrangements may be used. For example, the Koehler integrating optics may be arranged to optionally direct the processed light directly to the inlet port via one or more transponders or other optical arrangements discussed below.

[0078] for Figure 1 ,exist Figure 2 In this configuration, analyzer 50 is arranged to receive spectral data (including detected spectral features such as peak position and intensity) from spectrometer 26 and determine one or more properties of sample 12 based on the detected spectral features. Typically, the apparatus may be arranged to perform Raman spectroscopy on the sample, such that the detected spectral features are Raman spectral features, but other types of spectroscopic methods, such as fluorescence, infrared absorption, or visible light reflectance spectroscopy, may be used.

[0079] Figure 1 and Figure 2 The Koehler integrator or Koehler integrating optics 100 can be implemented in various ways known to those skilled in the art. However, specific technical problems related to providing light from the sample to the spectrometer prompted the inventors to consider many specific arrangements to address some of these needs.

[0080] Therefore, it will now be described that can be achieved Figure 1 and Figure 2 Various methods of using the Koehler integrating optics 100. Figure 3 In this Koehler integrating optics 100, a collector 110 and a condenser 120 are included. The collector 110 is arranged to receive probe light scattered from a collection region 17 at the sample 12. Although in Figure 3 In this configuration, collector 110 receives the collected light directly from collection region 17, but this can also be achieved via one or more other optical elements or devices, such as telescopic devices, transponders, one or more mirrors, etc. (not shown). Collector 110 is arranged to form a virtual image 17' of the collection region at or near condenser 120.

[0081] The condenser 120 is then arranged to form an image, often referred to as a virtual image, at the output plane 114 of the Koehler integrating optics. The image formed at the output plane 114 is an image located at or near the intermediate plane 112 of the collector 110. Figure 3 In the middle, the output plane 114 is located Figure 1 The optical fiber bundle 32 is depicted at or near the incident surface 34. However, the output plane can alternatively be the plane used as the input plane of a transponder or other additional optics, which in turn images the output plane onto the incident surface 34 of the optical fiber bundle, or the condenser 120 or other transponder or other optics can form an image of the intermediate plane at or near the inlet port 28 of the spectrometer itself.

[0082] The Koehler integrating optics 100 may be provided with a condenser stop 116 located at or in front of the condenser 120. This condenser stop can be used to limit the size of the virtual image 17' of the collection area formed at the condenser and to exclude unwanted light to prevent degradation of the image of the intermediate plane formed at the output plane. For this purpose, the condenser stop 116 can be used to define the perimeter of the virtual image 17' of the collection area 17 formed at or near the condenser, thereby helping to define the effective range of the collection area itself. However, this can be additionally or alternatively defined by other stops within the collection optics 20.

[0083] Collector 110 and condenser 120, as well as other optical elements of the Koehler integrating optics, may each be provided by a single lens, a compound lens, or a combination of such a single lens and / or compound lens, wherein each lens may have a spherical or aspherical shape depending on the design details.

[0084] In a typical implementation, the focal length and optical diameter of collector 110 can be approximately 25 mm and 15 mm, respectively. In order to effectively input the collected light into an optical fiber bundle with a high effective aperture, the focal length and optical diameter of condenser 120 can be much smaller, for example, approximately 3 mm and 3 mm, respectively, giving an effective numerical aperture of approximately 2.5.

[0085] Depending on the type of spectrum achieved by device 10, it may be desirable to include one or more spectral filters within the collecting optics 20, and conveniently within the Koehler integrating optics. For example, if the device is to perform Raman spectroscopy on a sample, it would typically be very necessary to provide one or more spectral filters that exclude the wavelength of the original laser from entering the spectrometer, but allow the wavelength of interest in Raman scattering to pass through. For this purpose, a notch filter that excludes the original laser or a more general low-pass filter can be used, but various other types of spectral filters may be used as appropriate.

[0086] Typically, such spectral filters can be holographic or dielectric (multilayer) type, and thus the spectral properties of the filter depend to some extent on the angle of incidence of light at the filter. This makes it important to place such filters in the region of a collecting optics where the light is fairly well collimated in order to avoid introducing spectral and other artifacts. Furthermore, if two or more of these filters are used, and if they are spaced further apart, for example, by a distance of about the diameter of each filter or greater, they generally work more effectively.

[0087] For this purpose, the collecting optics 20 may include one or more sets of collimating lenses and one or more spectral filters disposed within each set of collimating lenses, each set of collimating lenses being arranged such that the collected light is at least partially collimated as it passes through the one or more spectral filters disposed within the set. The required collimation may typically need to be within a range of about 2 to 3 degrees off the optical axis in order to largely avoid the adverse effects of decollimation, but other amounts of collimation (e.g., within about 5 degrees) may be used depending on the design limitations of the specific device.

[0088] Figure 4 It shows the Figure 3 The arrangement is modified so that a set of collimating lenses is formed using collimating lenses 130 included in collector 110, and one or more of the spectral filters 132 are also included in the collector, located between the collimating lenses 130. Using this arrangement, the collector serves both to form a virtual image of the collection region at condenser 120 or condenser stop 116 and to provide sufficient optical collimation within collector 130 to allow the spectral filters 132 to perform their functions adequately.

[0089] exist Figure 4In this arrangement, the collector 110 can therefore be implemented using a pair of simple or compound collimating lenses 130, wherein the one or more spectral filters are located between the lenses. Each collimating lens may, for example, have a focal length of about 30 mm and an optical diameter of about 25 mm, and the collimating lenses may typically be spaced about 100 mm apart to provide sufficient space for the spectral filters 132 to operate effectively.

[0090] If you want to use two or more spectral filters, then Figure 4 The arrangement tends to extend the length of the Koehler integrating optics longer than desired in order to maintain sufficient spacing between the spectral filters. Figure 5 It shows the Figure 4 and Figure 5 The arrangement can be modified such that one or more spectral filters 132 are optionally included within the collector, for example, between collimating lenses 130 included in collector 110, and one or more additional spectral filters 142 are included within an output transponder 140 arranged to forward the output plane 114 of the Koehler integrating optics to a second output plane 144, which may be located, as shown, at the incident surface 34 of the fiber bundle 32, or directly at the inlet port 28 of the spectrometer. The output transponder may, for example, include a collimating lens 146, with the one or more additional spectral filters 142 located between these collimating lenses. This arrangement allows for greater separation of the spectral filters 132, 142, although achieving adequate collimation of light within the output transponder may be difficult to achieve next to a reasonably high numerical aperture entering the second output plane 144.

[0091] Figure 5 The layout is still lacking Figure 3 and Figure 4 The condenser aperture seen in the image lacks some other arrangements for limiting the collection area (such as the aperture near the sample itself). The one or more spectral filters 132 within collector 110 can allow a large amount of high-incident-angle laser wavelength light from various surfaces in the collection optics (such as lens edges or anodized surfaces) to be scattered through the system. For this reason, in Figure 5 In this configuration, an optional sample aperture 148 is located near the sample 12 to help prevent stray probe light from outside the collection area 17 from entering the collection optics.

[0092] In certain implementations, such as when the sample is held in free space in front of the collecting optics 20 by a manipulator, it is inconvenient or undesirable to use the sample aperture 148 or other arrangements close to the sample to block unwanted probe light. Therefore, Figure 6Further modifications that can be applied to any of the previous arrangements are shown, wherein the sample aperture 148 is separated from the sample by a sample transponder 150, which is arranged to form a virtual image of the sample 12 at the sample aperture 148, thereby helping to define the extent of the collection area 17 on the sample 12 and prevent light from propagating further through the collection optics from outside the collection area.

[0093] Sample transponder 150 can be combined with the above. Figure 5 The output transponder 140 discussed is constructed in a similar manner, for example, including a collimating lens 156 and one or more spectral filters 152 located between the collimating lenses. However, in other embodiments, a single simple or compound lens may be used to provide the sample transponder 150. Similarly, in Figure 6 In this embodiment, collector 110 is shown to include a collimating lens 130 and one or more spectral filters 132 located between the collimating lenses, but may alternatively use a single simple or compound lens.

[0094] In Figure 6 In a corresponding example implementation, the first collimating lens 156 of the sample transponder 150 may have a focal length of approximately 60 mm (to provide the desired spacing from the sample) and an optical diameter of approximately 25 mm, and the second collimating lens may have a focal length of approximately 35 mm and an optical diameter of approximately 25 mm. The first and second collimating lenses 130 of the collector 110 may then each have a focal length of approximately 30 mm and a diameter of approximately 25 mm, and the individual lenses of the condenser may have a focal length and diameter of approximately 3 mm, wherein these small values ​​are used to provide a sufficiently high numerical aperture of approximately 2.5 at the output plane 114 for coupling (if necessary, via another transponder) into the fiber bundle or directly into the spectrometer's inlet port.

[0095] Overall Figure 1 and Figure 2 The Koehler integrating optics shown can be implemented in various other ways. Using conventional single-aperture lenses in the collector and condenser results in a slight deviation in the light intensity distribution across the output plane, which follows an approximately Gaussian distribution. Alternatively, lenses such as... Figure 7The arrangement shown mitigates this effect, wherein collector 110 includes a collector microlens array 170, and condenser 120 includes a condenser microlens array 172. The two microlens arrays are matched such that each microlens in one array corresponds to a microlens in the other array, and these arrays generally have the same size and optical properties. More specifically, the two microlens arrays can be confocal, such that each microlens in each array is located at or near the focal point of the corresponding microlens in the other array. In effect, the microlens arrays 170, 172 perform secondary sampling of the apertures of the collector and condenser, and these secondary samples are then superimposed again at the output plane 114, thereby additionally blending different portions of the collection region onto the output plane.

[0096] Typically, the collector microlens array 170 can follow the collector lens 174 within the collector 110 to perform secondary sampling of the aperture of the collector lens 174, while the condenser microlens array 172 can similarly precede the condenser lens 176 within the condenser. One or more spectral filters 178 can be disposed in one or both of the collector 110 and the condenser 120, preferably before and / or after the microlens array in the collector and condenser, as shown below. Figure 7 As shown.

[0097] Matching microlens arrays can be linear arrays, for example, from 3x3 to 5x5 microlenses. Using more microlenses in each array provides higher performance in terms of aperture resampling and superimposing resampling on the output plane; however, because accurate alignment of the microlenses is important for maintaining luminous flux, further increasing the number of microlenses makes construction more difficult. Microlens arrays can alternatively be hexagonally packaged or otherwise arranged, typically comprising about 5 to 30 microlenses.

[0098] Figure 7 The arrangement of the small lens array shown can be combined with various other construction details already discussed above. If Figure 5 The output transponder depicted, when used with a small lens arrangement, may ideally include an output plane stop at the output plane 114 in front of the output transponder, which may include one or more spectral filters as discussed above. Figure 6 The sample transponder depicted may also be used in conjunction with the described small lens array to achieve one or both of the sample aperture 148 between the sample transponder and the collector, and the spectral filter 152 within the sample transponder.

[0099] Figure 8 The process of irradiating the opposite side of a tablet with an infrared laser is described, using a method similar to... Figure 1 and Figure 3 The arrangement of the sampled light from the collection area of ​​the tablet (using trazodone (RTM) tablets) is shown in the results. This includes similar... Figure 3 The Koehler integrating optics 100 includes a collection optics 20 comprising a bundle of optical fibers, and the Koehler integrating optics 100 is arranged to process light from the collection region of the tablet and guide the processed light onto the incident surface 32 of the bundle. Instead of coupling the other end of the fiber bundle to a spectrometer, the intensity of light emitted from each fiber at the exit surface 36 is measured.

[0100] It is noteworthy that the collecting optics are arranged such that the Koehler integrating optics can be included or excluded in the collection of light from the tablet without altering the shape or size of the collecting region. This is achieved by ensuring that the collecting region has equivalent illumination in both cases, thus keeping the captureable photon flux constant. When the Koehler integrating optics are excluded, in “imaging” mode, the collecting optics directly form an image of the collecting region 17 onto the incident surface 32 of the beam.

[0101] More in detail, Figure 8 A graph is presented, where the X-axis corresponds to each of the eight optical fibers present in the bundle, and the y-axis corresponds to the detected light intensity (arbitrary unit) emitted from each fiber at exit surface 36. Each of the two solid lines depicts the intensity measured without using the Koehler integrating optics (imaging mode) when the collection area is precisely aligned with the center of the tablet (labeled "0 mm" and denoted as "x"), and the second line depicts the case when the collection area is moved a small distance of 1 mm from that position (labeled "1 mm" and denoted as "o"). The dashed lines depict the corresponding measurements using the Koehler integrating optics (Koehler mode).

[0102] It can be seen that although there is a significant loss in total intensity when using the Koehler integrating optics, the light intensity measured at any fiber between the two collection area locations exhibits very high consistency. When the Koehler integrating optics are not used, even if the current movement of the collection area is very small, the resulting intensity at each fiber will vary considerably, and the degree of variation differs greatly between different fibers.

[0103] Note that in this experiment, even with the use of Koehler integrating optics, the intensity varies considerably from one fiber to another. This variation is likely due to the use of off-the-shelf and unoptimized lenses, which introduce a degree of mechanical misalignment and can therefore be easily improved. However, because this variation is a constant effect, it does not affect the consistency of spectral measurements between different samples.

[0104] For a larger number (27 in total) of trazodone tablets, and at multiple different offset positions and orientations of the collection optics relative to each tablet, the process was repeated. Figure 8 The experiment shown in the paper demonstrates that, although there is a significant loss of strength in each fiber, the consistency of strength at each fiber is improved by about 10 times when the tablet is moved and different tablets are used, by using Koehler integrating optics.

[0105] This invention provides the construction methods and operating methods of the apparatus described herein, as well as corresponding methods for analyzing one or more samples. Figure 9 This method has been demonstrated, but any of the process steps and operations discussed above can be implemented in this method.

[0106] exist Figure 9 In step 210, the probe light is directed to sample 12. The probe light can be a laser probe light, or some other probe light suitable for performing the desired spectroscopic methods discussed above. Then, in step 220, the probe light scattered from sample 12 is collected. The collection of the probe light can be arranged such that the probe light has been scattered forward through the sample (in a transmission geometry) or in other ways as described above. Scattering can involve various spectral processes, such as Raman scattering, infrared absorption, etc.

[0107] At step 230, the collected probe light is processed to remove some or all of the spatial information from the sample. This can be described as removing image information about the collection area of ​​the sample, or in other ways described above, and in particular, Koehler integration can be used in this process. Typically, in this process, light from each point on the collection area of ​​the sample is mixed with light from other points on the collection area to distribute it across some or all of the output of the process.

[0108] Then, at step 230, the processed collected light is transmitted to a spectrometer, and the spectrometer is used to detect the spectral characteristics of the collected light. Typically, the processed light can be transmitted to an extended access port (such as a slit in the spectrometer), which is usually a dispersive spectrometer implemented using a diffraction grating or the like. Because such spectrometers are susceptible to small variations in wavelength response or calibration along the access port or slit, providing collected light (in which the spatial information of the sample has been removed) improves the consistency of the spectral response of the device under slight sample movement or geometric changes.

[0109] Then, at step 250, the spectral characteristics (such as full or partial spectra) output by the spectrometer, or the properties of a single characteristic (such as one or more specific peak intensities), are used to determine one or more properties of the sample (such as the presence or measurement of one or more chemical components). At step 260, information related to such properties, such as an alert indicating that the properties fall outside the expected range, is output.

[0110] Some aspects of the described devices and methods can be implemented using computer program code that executes on one or more suitable computer systems. Such a computer system typically includes one or more microprocessors for executing such computer program code, memory for storing such program and related data, and suitable input and output facilities that may include, for example, wired or wireless data connections, non-volatile storage devices, and visual displays, and input devices such as keyboards and mice (if desired).

[0111] For example, such as Figure 1 and Figure 2 The described analyzer 50 may include one or more suitable computer systems programmed with appropriate software to receive Raman spectral features S from the spectrometer 26, analyze and process those spectral features in various ways (e.g., noise reduction, conversion to a desired form, and measurement of specific spectral features), and match specific spectral features with known or expected components or properties of the sample to determine the properties P of the sample. A library of spectral features that can be used for such comparisons may be obtained, for example, from STMicroelectronics or Sigma-Aldrich.

[0112] Although various embodiments of the invention have been described, those skilled in the art will recognize that many different modifications and variations can be made to these embodiments without departing from the scope of the invention.

Claims

1. An apparatus for performing spectral analysis on a sample, wherein the sample is a pharmaceutical dosage form, the apparatus comprising: A transfer optics is arranged to guide the probe light to the transfer area of ​​the sample; A collection optics is arranged to collect probe light scattered from a collection area of ​​the sample; as well as A spectrometer having an inlet port, the spectrometer being arranged to receive collected probe light from the collecting optics at the inlet port of the spectrometer and to detect the spectral characteristics of the received probe light. The collecting optics include a Koehler integrating optics device, which is arranged to process the collected probe light. The collecting optics includes an optical fiber bundle having: an incident surface arranged to receive the collected probe light after processing by the Koehler integrating optics; and an exit surface arranged to transmit the collected probe light to the port of the spectrometer. The Koehler integrating optics therein collects and processes the scattered light such that the collected light from each point in the collection region is distributed on the inlet port of the spectrometer.

2. The apparatus of claim 1, further comprising an analyzer arranged to determine one or more properties of the sample from detected spectral features.

3. The device according to claim 1 or 2, wherein, The detected spectral features are Raman spectral features.

4. The device according to claim 1 or 2, wherein, The collection area is separated from the transmission area.

5. The device according to claim 4, wherein, The collection area is on the side of the sample opposite to the transfer area.

6. The device according to claim 1 or 2, wherein, The Koehler integrating optics includes a collector arranged to receive the collected light from the collection region of the sample, and a condenser arranged to receive the collected light from the collector.

7. The device according to claim 6, wherein, The Koehler integrating optics defines an intermediate plane at or near the collector and an output plane, the collector being arranged to form an image of the collection region of the sample at or near the condenser, and the condenser being arranged to form an image of the intermediate plane at the output plane.

8. The device according to claim 7, wherein, The collecting optics includes a bundle of optical fibers having an incident surface arranged to receive the collected probe light after being processed by the Koehler integrating optics. The output plane is arranged to transmit the collected probe light to the port of the spectrometer, and the output plane is located at or near the incident plane.

9. The device according to claim 6, wherein, The collecting optics includes one or more sets of collimating lenses and one or more spectral filters disposed within each set of collimating lenses, each set of collimating lenses being arranged such that the collected light is collimated as it passes through the one or more spectral filters disposed within the set.

10. The device according to claim 9, wherein, A set of the collimating lenses are lenses of the collector, and one or more of the spectral filters are included within the collector.

11. The device according to claim 9 or 10, wherein, A set of the collimating lenses is included in an output transponder arranged to forward an image from the output plane of the condenser, and one or more of the spectral filters are included within the output transponder.

12. The device according to claim 9, wherein, A set of collimating lenses is included in a sample transponder arranged to form a transponded virtual image of the collection region for imaging by the collector, and one or more of the spectral filters are included within the sample transponder.

13. The apparatus of claim 12, further comprising a sample aperture between the sample transponder and the collector, the sample transponder being arranged to form the transponded virtual image of the collection region at the sample aperture.

14. The device according to any one of claims 9 to 10, wherein, The detected spectral feature is a Raman spectral feature, the probe light guided to the transfer region of the sample has one or more probe wavelengths, and the one or more spectral filters include spectral filters arranged to block light of the probe wavelengths but allow light of the Raman spectral feature to pass through.

15. The apparatus of claim 6, further comprising a sample aperture and a sample transponder, the sample transponder being arranged to form a transponded virtual image of the collection region at the sample aperture for imaging by the collector.

16. The device of claim 6, further comprising a condenser stop at or near the condenser, such that the condenser stop limits the extent of the virtual image of the collection region formed by the collector at or near the condenser.

17. The device according to claim 6, wherein, The collector includes a collector microlens array, and the concentrator includes a concentrator microlens array.

18. The device according to claim 17, wherein, The collector and the condenser microlens array are confocal, such that the microlens array performs secondary sampling on the apertures of the collector and the condenser, and the secondary sampling is superimposed at the output plane.

19. The device according to claim 1, wherein, The drug dosage form is one or more of the following: tablets; coated tablets; capsules; and soft capsules.

20. The device according to claim 1 or 2, wherein, The drug dosage form has one or more of the following features: surface markings; grooves; embossing; multiple surface areas, each with a different color; and imprints.

21. A method for performing spectral analysis on a sample, wherein the sample is a pharmaceutical dosage form, the method comprising: The probe light is directed to the transfer area of ​​the sample; Collect probe light from the collection area of ​​the sample; The collected probe light is processed by the Koehler integrating optics, such that the collected light from each point in the collection area is distributed on the inlet port of the spectrometer by receiving the collected probe light collected at the incident surface of an optical fiber after being processed by the Koehler integrating optics. as well as The processed, collected probe light from the exit surface of the optical fiber is transmitted to the inlet port of the spectrometer.

22. The method according to claim 21, wherein, Processing the collected probe light involves applying Koehler integrals to the collected probe light.

23. The method according to claim 21 or 22, further comprising: The spectrometer detects one or more spectral properties of the collected and processed light; as well as One or more properties of the sample are determined from the detected spectral properties.

24. The method according to claim 23, wherein, The one or more spectral properties are Raman spectral properties.

25. The method according to any one of claims 21 to 22, wherein, The transfer area is on the side of the sample opposite to the collection area.

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