Endoscopic detector system, composite optical fibre, endoscopic system and method for examining a sample
The endoscopic detector system with a multimode optical fiber and selective light detection enhances imaging contrast and resolution, addressing the limitations of existing holographic endoscopes by filtering unwanted light and using coherent or pulsed light modulation for faster image acquisition.
Patent Information
- Application Number
- PCT/EP2025/057860
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-03-22
- Filing Date
- 2025-03-21
- Publication Date
- 2025-09-25
AI Technical Summary
Existing holographic endoscopes face challenges in achieving high-contrast, high-resolution imaging with fast imaging speeds, especially when using pulsed laser light for biomedical applications.
An endoscopic detector system comprising a multimode optical fiber with a focusing element and a detector unit that selectively detects light at predetermined angles, combined with a gradient-index lens or other focusing elements, to enhance axial resolution and contrast by filtering out unwanted light, and an illumination device using coherent or pulsed light modulation to illuminate specific points in the sample.
The system achieves improved imaging contrast and resolution, allowing for faster image acquisition with reduced noise and numerical artifacts, particularly suitable for detailed observations of delicate tissue structures.
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Figure EP2025057860_25092025_PF_FP_ABST
Abstract
Description
[0001] Endoscopic detector system, composite optical fiber, endoscopic system and method for examining a sample
[0002] Technical area
[0003] The invention relates to endoscopic examinations using a multimode optical fiber, in particular using holographic endoscopy. In particular, the invention relates to an endoscopic detector system, a composite optical fiber, an endoscopic system, and a method for examining a sample using an endoscopic system.
[0004] Background of the invention
[0005] Holographic endoscopes, which utilize the controlled transport of light through hair-thin multimode optical fibers, are used, among other things, for minimally invasive observations in biomedical applications. This concept is based on complex media photonics, which leverages the empirical quantification of optical propagation through a random medium and enables applications not possible with conventional endoscopes. Holographic endoscopy utilizes wavefront shaping technology (using spatial light modulators) to shape light propagating through otherwise random multimode optical fibers to achieve any desired light output. For example, detailed images can be obtained from great depths of delicate tissue structures, such as neurons.
[0006] Summary of the invention
[0007] The object of the invention is to propose an endoscopic detector system, a composite optical fiber, an endoscopic system, and a method for examining a sample using an endoscopic system, which are further improved over known holographic endoscopes and, in particular, enable even better images, especially images with higher contrast, with better axial resolution, with faster imaging, and / or with additional imaging options when using pulsed laser light. This object is achieved by the subject matter of the independent patent claims. Further developments of the invention emerge from the subclaims and the following description.
[0008] One aspect of the invention relates to an endoscopic detector system. The endoscopic detector system comprises an optical fiber array and a detector unit. The optical fiber array comprises a multimode optical fiber and a focusing element.
[0009] A multimode optical fiber is understood to be an optical fiber or optical waveguide that has a fiber core whose diameter is large enough to allow multiple light modes, in particular hundreds to hundreds of thousands of light modes, to propagate within it. This naturally depends on the wavelength of the light to be used, with light typically being in the visible spectrum, i.e., with wavelengths in the range from approximately 380 nm to 750 nm, and / or in the near infrared spectrum, with wavelengths in the range from approximately 750 nm to 1.5 pm. In the context of the present invention, the terms optical fiber or optical waveguide can therefore also be used as a synonym for the term multimode optical fiber, provided the fiber core has a sufficiently large diameter.In particular, the multimode optical fiber is a step-index fiber, meaning that the fiber core has one refractive index and the cladding of the multimode optical fiber has a different refractive index. This refractive index changes stepwise at the transition from the fiber core to the cladding, and the refractive index of the cladding is lower than the refractive index of the fiber core. It is also possible for the step-index fiber to have additional layers, with the refractive index changing stepwise between each layer.
[0010] The multimode optical fiber has an optical axis. Assuming a straight, non-bent multimode optical fiber, the optical axis coincides with the axis of rotational symmetry of the multimode optical fiber. The optical axis therefore extends in a longitudinal direction of the multimode optical fiber, so that the multimode optical fiber appears circular in a cross-section perpendicular to the optical axis. Furthermore, the multimode optical fiber has a proximal end and a distal end opposite the proximal end. The distal end of the multimode optical fiber can be inserted into a sample and / or brought close to a sample. The sample can be an inorganic or an organic sample, for example an animal or a human.
[0011] The focusing element is located at the distal end of the multimode optical fiber. It can be configured to focus light emerging from the multimode optical fiber and to convert light emitted from a point on the sample that lies at the focus of the focusing element into a collimated light beam and feed this collimated light beam into the distal end of the multimode optical fiber.
[0012] The detector unit is arranged at the proximal end of the multimode optical fiber and is designed to separately detect light emerging from the multimode optical fiber at the proximal end at one or more predetermined angles to the optical axis. This light can be emitted from a point on the sample, converted into a collimated light beam by the focusing element, and guided through the multimode optical fiber. In order to be converted into a collimated light beam by the focusing element, the point on the sample must be in a focal plane of the focusing element. The collimated light beam then has an angle to the optical axis of the multimode optical fiber that depends on the distance of the point from the optical axis. The greater the distance of the point from the optical axis, the greater the angle of the collimated light beam to the optical axis.An axial component of the light's k-vector is a propagation constant, meaning that the axial component of the k-vector is maintained from the point of entry into the multimode optical fiber until the point of exit. This is particularly pronounced in step-index fibers. Since the axial component of the k-vector is related to the angle of the light to the optical axis, light entering the multimode optical fiber at a specific angle to the optical axis of the multimode optical fiber exits the multimode optical fiber as a light cone. The aperture angle of the light cone to the optical axis is equal to the specific angle, which in turn depends on the distance of the point on the sample that emits the light from the optical axis.If only the light emerging at the predetermined angle to the optical axis is detected by the detector unit, then only light from points that are at the same distance from the optical axis as the point on the sample to be viewed is detected. The light from points that are at a different distance from the optical axis is not detected. This selective detection achieves a high contrast in the endoscopic detector system. The same applies if only the light emerging at several predetermined angles to the optical axis is detected by the detector unit. Then only light from points that are at the same distance from the optical axis as several points on the sample to be viewed is detected.If these multiple points are far enough apart from each other and have different distances from the optical axis, a high contrast of the endoscopic detector system is also achieved and by examining several points at the same time, the total examination time can be shortened.
[0013] In some embodiments, the optical fiber arrangement further comprises a light-reflecting surface. This light-reflecting surface is arranged at the distal end of the multimode optical fiber and / or on the focusing element. The angle between the normal to the light-reflecting surface and the optical axis of the multimode optical fiber at the distal end is between 30° and 60°, in particular between 40° and 50°. The light-reflecting surface deflects light propagating along the optical axis in the multimode optical fiber in a direction radial to the optical axis. In particular, the light is deflected by 90° if the light-reflecting surface is inclined by 45° to the optical axis. Thus, regions of the sample that lie radially to the optical axis at the distal end of the multimode optical fiber can be examined.The above description of the angles to the optical axis also applies to this embodiment, in which case the angles in the multimode optical fiber are to be understood and / or the optical axis is deflected at the light reflection surface.
[0014] The light reflection surface can be used in particular in conjunction with a light transmission surface. This light transmission surface can run essentially parallel to the optical axis, i.e. an angle between the optical axis and the light transmission surface can be less than 15°, in particular less than 10°, most particularly less than 5°. The light transmission surface can be designed to transmit light radially to the optical axis. This means that light can both exit the multimode optical fiber through the light transmission surface and light from outside the multimode optical fiber can enter the multimode optical fiber through the light transmission surface. This light transmission surface can be a flat surface or can be designed such that it forms the focusing element.
[0015] The light-reflecting surface and / or the light-transmitting surface can be produced by polishing or milling the distal end of the multimode optical fiber and / or the focusing element, wherein the milling can be carried out, in particular, with a focused ion beam or by laser ablation. Furthermore, the light-transmitting surface can be provided with a coating, in particular with a dielectric coating, to increase the transmission coefficient. Furthermore, the light-reflecting surface can be provided with a coating, in particular with a dielectric and / or metallic coating, to increase the reflection coefficient.
[0016] In some embodiments, the focusing element is a gradient index lens. The gradient index lens is, in particular, a multimode optical fiber with a gradient profile of a quarter-pitch length or shorter. The gradient index lens can, in particular, be connected to the multimode optical fiber to form a composite optical fiber. The connection can be made, for example, by splicing. In particular, an outer diameter of the gradient index lens can be selected to be the same size as an outer diameter of the multimode optical fiber, so that a particularly uniform composite optical fiber is obtained. If a light reflection surface is provided, this can be integrated into the gradient index lens, in particular at an end of the gradient index lens that is opposite the end of the gradient index lens that is connected to the multimode optical fiber.
[0017] Alternatively, the focusing element is a spherical lens, a plano-convex lens, or a Fresnel lens. These lenses can be spliced, glued, printed, etched, or fused to the distal end of the multimode optical fiber. In some embodiments, the detector unit comprises a detector array configured to selectively detect light in one or more annular regions corresponding to one or more predetermined angles. If light emerges from the multimode optical fiber as a cone of light at the predetermined angle, which, as described above, corresponds to the distance of the light-emitting point from the optical axis, it is detected by the detector array in the annular region.However, if light is emitted from a different point at a different distance from the optical axis, this light is emitted into a ring-shaped area with a different radius and is not detected by the detector array. This unwanted light is thus filtered out, thus increasing the contrast of the detector system.
[0018] In some embodiments, the detector unit further comprises an additional focusing element facing the proximal end of the multimode optical fiber. This additional focusing element can be configured as a lens. The additional focusing element focuses the light emerging from the multimode optical fiber at one or more predetermined angles onto one or more annular regions in a focal plane of the additional focusing element. This further increases the angular resolution of the detector unit, and the detector arrangement can be designed more compactly.
[0019] In some embodiments, the detector arrangement comprises a selection element for selecting the one or more annular regions. If the detector unit comprises the further focusing element, the selection element is arranged in particular at the focus of this further focusing element. Furthermore, the detector arrangement comprises a detector element for detecting the light arriving in the selected one or more annular regions. The selection element can be an annular aperture. The annular aperture can be adapted to different radii of the annular regions; for example, different annular apertures with different radii can be interchangeable.In this case, the detector element is arranged on the side of the selection element facing away from the proximal end of the multimode optical fiber and / or the additional focusing element, so that light transmitted through the aperture strikes the detector and is registered by it. Alternatively, the selection element can be an annular mirror that only reflects light arriving in an annular region. The detector is then arranged on the same side of the selection element as the proximal end of the multimode optical fiber and / or the additional focusing element. A variable annular mirror can be implemented, for example, as a micromirror array. These variants of the detector arrangement are particularly easy and cost-effective to manufacture.
[0020] Alternatively, the detector arrangement comprises a detector element designed to selectively detect light in the one or more annular regions. If the detector unit comprises the further focusing element, the detector element is arranged in particular at the focus of the further focusing element. The detector element can, for example, have annular detector regions. Alternatively, the detector element can comprise a grid arrangement with individual pixels arranged in rows and columns, in which case only the pixels that lie on an annular region with a predetermined radius are evaluated for selectively detecting the light. This allows different annular regions to be examined quickly and easily.
[0021] Another aspect of the invention relates to a composite optical fiber. This composite optical fiber comprises a multimode optical fiber having an optical axis, a proximal end, and a distal end, and a gradient-index lens connected to the distal end of the multimode optical fiber.
[0022] A multimode optical fiber is understood to be an optical fiber or optical waveguide that has a fiber core whose diameter is large enough to allow multiple light modes, in particular hundreds to hundreds of thousands of light modes, to propagate within it. This naturally depends on the wavelength of the light to be used, with light typically being in the visible spectrum, i.e., with wavelengths in the range from approximately 380 nm to 750 nm, and / or in the near infrared spectrum, with wavelengths in the range from approximately 750 nm to 1.5 pm. In the context of the present invention, the terms optical fiber or optical waveguide can therefore also be used as a synonym for the term multimode optical fiber, provided the fiber core has a sufficiently large diameter.In particular, the multimode optical fiber is a step-index fiber, meaning that the fiber core has one refractive index and the cladding of the multimode optical fiber has a different refractive index. This refractive index changes stepwise at the transition from the fiber core to the cladding, and the refractive index of the cladding is lower than the refractive index of the fiber core. It is also possible for the step-index fiber to have additional layers, with the refractive index changing stepwise between each layer.
[0023] The optical axis of the multimode optical fiber coincides with the axis of rotational symmetry of the multimode optical fiber if the multimode optical fiber is straight, i.e., not bent. The optical axis thus extends in a longitudinal direction of the multimode optical fiber, so that the multimode optical fiber appears circular in a cross-section perpendicular to the optical axis. In a bent multimode optical fiber, the optical axis is bent according to the bend of the multimode optical fiber.
[0024] The distal end of the multimode optical fiber is opposite the proximal end and can be inserted into and / or brought close to a sample. The sample can be an inorganic or organic sample, such as an animal or a human.
[0025] The gradient index lens may be configured to focus light coming from the multimode optical fiber and to convert light emitted from a point on the sample that is in the focus of the gradient index lens into a collimated light beam and to feed this collimated light beam into the distal end of the multimode optical fiber.
[0026] The gradient index lens can, in particular, be a multimode optical fiber with a gradient profile of a quarter-pitch length or shorter. It can be connected to the multimode optical fiber, for example, by splicing. In particular, an outer diameter of the gradient index lens can be selected to be the same size as an outer diameter of the multimode optical fiber, so that a particularly uniform composite optical fiber is obtained. The composite optical fiber can be used in an endoscopic detector system according to the above description, so that a high resolution of the endoscopic detector system can be achieved with the aid of the composite optical fiber.
[0027] In some embodiments, the gradient index lens has a light-reflecting surface. This light-reflecting surface is arranged at one end of the gradient index lens, which is opposite the end of the gradient index lens connected to the multimode optical fiber. The angle between the normal to the light-reflecting surface and the optical axis of the multimode optical fiber at the distal end is between 30° and 60°, in particular between 40° and 50°. The light-reflecting surface deflects light propagating along the optical axis in the multimode optical fiber in a direction radial to the optical axis. In particular, the light is deflected by 90° if the light-reflecting surface is tilted by 45° to the optical axis. Thus, regions of the sample that lie radially to the optical axis in the region of the gradient index lens can be examined.
[0028] The light reflection surface can be used in particular in conjunction with a light transmission surface. This light transmission surface can run essentially parallel to the optical axis, i.e. an angle between the optical axis and the light transmission surface can be less than 15°, in particular less than 10°, most particularly less than 5°. The light transmission surface can be designed to transmit light radially to the optical axis. This means that light can both exit from the composite optical fiber through the light transmission surface and light from outside the composite optical fiber can enter the composite optical fiber through the light transmission surface. This light transmission surface can in particular be a flat surface.
[0029] The light-reflecting surface and / or the light-transmitting surface can be produced by polishing or milling the end of the gradient-index lens opposite the end of the gradient-index lens connected to the multimode optical fiber, wherein the milling can be performed, in particular, with a focused ion beam. Furthermore, the light-transmitting surface can be provided with a coating, in particular a dielectric coating, to increase the transmission coefficient. Furthermore, the light-reflecting surface can be provided with a coating, in particular a dielectric and / or metallic coating, to increase the reflection coefficient.
[0030] Another aspect of the invention relates to an endoscopic system. The endoscopic system comprises an illumination device and the endoscopic detector system according to the preceding description.
[0031] The illumination device is designed to illuminate a sample or part of a sample. This sample can be an inorganic or organic sample, for example, an animal or a human.
[0032] The endoscopic system achieves high contrast due to the endoscopic detector system mentioned.
[0033] In some embodiments, the illumination device is designed to illuminate a light sheet. This light sheet extends, in particular, perpendicular to the optical axis, can be generated by a laser, and intersects the sample. The fluorescence emitted by the sample is then detected by the endoscopic detector system. Using a transfer matrix of the optical fiber arrangement, light points in the sample can then be inferred from the light detected by the endoscopic detector system. This is an inverse problem that can be solved, for example, using the maximum likelihood method.Since the present detector system can selectively detect points in the sample that are located on annular regions in the sample, noise coming from points outside these annular regions, which would otherwise influence the reconstruction algorithm, is suppressed, thus reducing numerical artifacts and improving the contrast of the obtained image.
[0034] Alternatively, the illumination device comprises a coherent light source and a light modulator. The coherent light source is, in particular, a laser. The coherent light source and the light modulator are configured such that the coherent light source emits coherent light, which is then pre-shaped by the light modulator and fed into the proximal end of the multimode optical fiber. The light modulation can be carried out, in particular, as amplitude, phase, and / or polarization modulation. The light modulation is carried out in particular such that one or a few points of the sample are illuminated. Thus, only this or these points in the sample are illuminated, and stray light is suppressed by the endoscopic detector system, so that particularly good contrast and thus particularly good image quality are achieved.If several points in the sample are illuminated, these points should be at different distances from the optical axis so that the light emitted by these points enters the multimode optical fiber at different angles and exits the multimode optical fiber at different angles, where it can then be differentiated by the detector unit. This enables the simultaneous illumination of several points, enabling faster endoscopic image acquisition. The light modulation required to illuminate a specific point can be determined, for example, by calculating a transmission matrix that describes the transfer of coherent light from one end of the optical fiber array to the other.This can be achieved, for example, by determining the light transfer from a large number of known points emitting coherent light. Using the transfer matrix, the modulation of the coherent light required to illuminate one or a few points in the sample is then determined.
[0035] A further aspect of the invention relates to another endoscopic system. This endoscopic system comprises an illumination device and an optical fiber arrangement.
[0036] The illumination device comprises a pulsed light source, in particular a pulsed coherent light source, most particularly a pulsed laser. Furthermore, the illumination device comprises a light modulator.
[0037] The optical fiber assembly comprises a multimode optical fiber and a focusing element.
[0038] A multimode optical fiber is understood to be an optical fiber or optical waveguide that has a fiber core whose diameter is large enough to allow multiple light modes, in particular hundreds to hundreds of thousands of light modes, to propagate within it. This naturally depends on the wavelength of the light to be used, with light typically being in the visible spectrum, i.e., with wavelengths in the range from approximately 380 nm to 750 nm, and / or in the near infrared spectrum, with wavelengths in the range from approximately 750 nm to 1.5 pm. In the context of the present invention, the terms optical fiber or optical waveguide can therefore also be used as a synonym for the term multimode optical fiber, provided the fiber core has a sufficiently large diameter.In particular, the multimode optical fiber is a step-index fiber, meaning that the fiber core has one refractive index and the cladding of the multimode optical fiber has a different refractive index. This refractive index changes stepwise at the transition from the fiber core to the cladding, and the refractive index of the cladding is lower than the refractive index of the fiber core. It is also possible for the step-index fiber to have additional layers, with the refractive index changing stepwise between each layer.
[0039] The multimode optical fiber has an optical axis. Assuming a straight, non-bent multimode optical fiber, the optical axis coincides with the axis of rotational symmetry of the multimode optical fiber. The optical axis thus extends in a longitudinal direction of the multimode optical fiber, so that the multimode optical fiber appears circular in a cross-section perpendicular to the optical axis.
[0040] Furthermore, the multimode optical fiber has a proximal end and a distal end opposite the proximal end. The distal end of the multimode optical fiber can be inserted into a sample together with the focusing element and / or brought into proximity with a sample. The sample can be an inorganic or organic sample, for example, an animal or a human.
[0041] The focusing element is arranged at the distal end of the multimode optical fiber. It can be configured to focus light emerging from the multimode optical fiber and to convert light emitted from a point on the sample that lies at the focus of the focusing element into a collimated light beam and to feed this collimated light beam into the distal end of the multimode optical fiber. The light modulator is configured such that the pulsed light is fed into the proximal end of the multimode optical fiber at at least a predetermined angle to the optical axis. Since light fed into the multimode optical fiber at a certain angle propagates primarily within a mode group, with one mode group comprising modes that exhibit a similar propagation velocity, little or no intermodal dispersion occurs, so that the light pulse is preserved.If the light is applied at more than one predetermined angle, the light pulses are retained for the respective angles, allowing multiple points on a sample at different distances from the optical axis to be illuminated simultaneously. Furthermore, if the multimode optical fiber is a step-index fiber, a circular polarization state of the coherent light is also retained. Other microscopy techniques, such as fluorescence lifetime microscopy, STED (stimulated emission depletion) microscopy, or multiphoton microscopy, also benefit from the improved light pulses obtained in this way.
[0042] Furthermore, the lighting device can have apertures and / or lenses.
[0043] The endoscopic system may further comprise a detector. The detector may, for example, detect light emitted by the sample via fluorescence, entering the multimode optical fiber at the distal end, being guided by the multimode optical fiber, and exiting the multimode optical fiber at the proximal end. Alternatively, the detector may detect light emitted by the sample via fluorescence via another optical system. Examples of such a detector include a photodetector, a camera, a photon counter, in particular a photomultiplier, a hybrid photodetector, and a single-photon avalanche diode.
[0044] A further aspect of the invention relates to a method for examining a sample using an endoscopic system according to the preceding description.
[0045] In this method, the sample is illuminated by the illumination device. This illumination can be direct, such as with the light sheet, or it can be provided via the optical fiber array, in particular using pre-shaped light from the light modulator.
[0046] Before the sample is illuminated with the illumination device, it may be necessary to align the multimode optical fiber so that light emitted by the sample can enter the distal end of the multimode optical fiber. This alignment can be done manually or automatically, with the details of the alignment depending on the specific sample.
[0047] In response to illumination, the sample emits light, for example, through fluorescence. This emitted light then enters the distal end of the multimode optical fiber via the focusing element, is redirected by the multimode optical fiber, and finally exits the multimode optical fiber. The light exiting at one or more predetermined angles to the optical axis is then detected. By selectively detecting light exiting at one or more predetermined angles from points on the sample at one or more corresponding distances from the optical axis, the contrast and quality of an image obtained by this method is improved.
[0048] For confocal microscopy, a transmission matrix of the multimode optical fiber can also be determined with the focusing element. This can be achieved, for example, by determining the light transfer from a plurality of known points that emit coherent light. The light modulator is then controlled based on the transmission matrix such that the light illuminating the sample is focused at one or more points on the sample that correspond to the one or more predetermined angles to the optical axis. This enables scanning of one or more points in the sample. If only one point is illuminated at a time, the image quality can be improved by suppressing light that exits the multimode optical fiber at angles other than the predetermined angle to the optical axis.However, if multiple points are illuminated simultaneously at different distances from the optical axis, it is possible to differentiate between the multiple points by selectively detecting the light emerging from the multimode optical fiber at the corresponding angles to the optical axis and, at the same time, to improve the image quality by suppressing light emerging from the multimode optical fiber at angles to the optical axis other than the predetermined angles.
[0049] It is understood that a preferred embodiment can also be achieved from a combination of dependent claims with the respective independent claim.
[0050] For further clarification, the invention is described using embodiments illustrated in the figures. These embodiments are to be understood as examples only and not as limitations.
[0051] Short description of the characters
[0052] It shows:
[0053] Fig. 1 is a schematic longitudinal section through an embodiment of a composite optical fiber;
[0054] Fig. 2 shows a schematic longitudinal section through another embodiment of a composite optical fiber;
[0055] Fig. 3 shows a schematic longitudinal section through an embodiment of an endoscopic detector system;
[0056] Fig. 4 shows a schematic longitudinal section through another embodiment of an endoscopic detector system;
[0057] Fig. 5 is a schematic longitudinal section through yet another embodiment of an endoscopic detector system;
[0058] Fig. 6 shows a schematic longitudinal section through an embodiment of an endoscopic system;
[0059] Fig. 7 shows a schematic longitudinal section through another embodiment of an endoscopic system;
[0060] Fig. 8 is a schematic longitudinal section through yet another embodiment of an endoscopic system; and
[0061] Fig. 9 shows a schematic longitudinal section through yet another embodiment of an endoscopic system. Detailed description of the invention
[0062] In the figures, like reference numerals indicate either like elements or elements with equivalent functions. Elements that have already been described are not necessarily described again in subsequent figures.
[0063] Figure 1 shows a schematic longitudinal section through an embodiment of a composite optical fiber 1. The composite optical fiber 1 comprises a multimode optical fiber 2 with an optical axis 3, a proximal end 4 and a distal end 5, and a gradient index lens 6 connected to the distal end 5.
[0064] A multimode optical fiber 2 is understood to be an optical fiber or optical waveguide having a fiber core 7 whose diameter is large enough for multiple light modes, in particular hundreds to hundreds of thousands of light modes, to propagate therein. This naturally depends on the wavelength of the light to be used, with light typically being used in the visible spectrum, i.e., with wavelengths in the range from approximately 380 nm to 750 nm, and / or in the near infrared range, with wavelengths in the range from approximately 750 nm to 1.5 pm. Thus, in the context of the present invention, the terms optical fiber or optical waveguide can also be used as a synonym for the term multimode optical fiber 2, provided the fiber core 7 has a sufficiently large diameter.In particular, the multimode optical fiber 2 is a step-index fiber, which means that the fiber core 7 has one refractive index and a cladding 8 of the multimode optical fiber 2 has a different refractive index, wherein this refractive index changes stepwise at the transition from the fiber core 7 to the cladding 8 and wherein the refractive index of the cladding 8 is smaller than the refractive index of the fiber core 7. It is also possible for the step-index fiber to have further layers, wherein the refractive index changes stepwise between the individual layers.
[0065] The optical axis 3 of the multimode optical fiber 2 coincides with the axis of rotational symmetry of the multimode optical fiber 2 when the multimode optical fiber 2 is straight, i.e., not bent. The optical axis 3 thus extends in a longitudinal direction of the multimode optical fiber 2, so that the multimode optical fiber 2 appears circular in a cross-section perpendicular to the optical axis 3.
[0066] The distal end 5 of the multimode optical fiber 2 is opposite the proximal end 4 and, together with the gradient index lens 6, can be inserted into and / or brought close to a sample. The sample can be an inorganic or organic sample, for example, an animal or a human.
[0067] The gradient index lens 6 can be designed to focus light coming from the multimode optical fiber 2 and / or to convert light emitted from a point on the sample lying in the focal plane of the gradient index lens 6 into a collimated light beam and to feed this collimated light beam into the distal end 5 of the multimode optical fiber 2.
[0068] The gradient index lens 6 can, in particular, be a multimode optical fiber with a gradient profile of a quarter-pitch length or shorter. It can be connected to the multimode optical fiber 2, for example, by splicing or gluing. In particular, an outer diameter of the gradient index lens 6 can be selected to be the same size as an outer diameter of the multimode optical fiber 2, so that a particularly uniform composite optical fiber 1 is obtained.
[0069] Figure 2 shows a schematic longitudinal section through another embodiment of a composite optical fiber 1. Compared to the embodiment of Figure 1, in this embodiment the gradient index lens 6 has a light reflection surface 9. This light reflection surface 9 is arranged at one end of the gradient index lens 6, which is opposite the end of the gradient index lens 6 that is connected to the multimode optical fiber 2. An angle between the normal to the light reflection surface 9 and the optical axis 3 of the multimode optical fiber 2 at the distal end 5 is between 30° and 60°, in particular between 40° and 50°. The light reflection surface 9 deflects light propagating along the optical axis 3 in the multimode optical fiber 2 in a direction radial to the optical axis 3. In particular, the light is deflected by 90° when the light reflection surface 9 is inclined by 45° to the optical axis.Thus, areas of the sample that lie in the area of the gradient index lens 6 radial to the optical axis 3 can be examined.
[0070] The light reflection surface 9 can be used in particular in conjunction with a light transmission surface 10. This light transmission surface 10 can run essentially parallel to the optical axis 3, i.e., an angle between the optical axis 3 and the light transmission surface 10 can be less than 15°, in particular less than 10°, most particularly less than 5°. The light transmission surface 10 can be designed to transmit light radially to the optical axis 3. Thus, light can both exit from the composite optical fiber 1 through the light transmission surface 10 and light from outside the composite optical fiber 1 can enter the composite optical fiber 1 through the light transmission surface 10. This light transmission surface 10 can in particular be a flat surface.
[0071] The light-reflecting surface 9 and / or the light-transmitting surface 10 can be produced by polishing or milling the end of the gradient-index lens 6 that is opposite the end of the gradient-index lens 6 that is connected to the multimode optical fiber 2. The milling can be carried out, in particular, with a focused ion beam. Furthermore, the light-transmitting surface 10 can be provided with a coating, in particular with a dielectric coating, to increase the transmission coefficient. Furthermore, the light-reflecting surface 9 can be provided with a coating, in particular with a dielectric and / or metallic coating, to increase the reflection coefficient.
[0072] Figure 3 shows a schematic longitudinal section through an embodiment of an endoscopic detector system 11. The endoscopic detector system 11 comprises an optical fiber arrangement 1 shown as a composite optical fiber 1 according to the previous description and a detector unit 12.
[0073] In general, the optical fiber arrangement 1 can comprise a multimode optical fiber 2 and a focusing element 6. As an alternative to the gradient index lens 6, the focusing element 6 can also be a spherical lens, a plano-convex lens, or a Fresnel lens. These lenses can be spliced, glued, printed, etched, or fused to the distal end 5 of the multimode optical fiber 2. The detector unit 12 is arranged at the proximal end 4 of the multimode optical fiber 2 and is designed to separately detect light emerging from the multimode optical fiber 2 at the proximal end 4 at one or more predetermined angles to the optical axis 3. Light beam paths 13 emitted from a point 14 offset from the optical axis 3 are shown as black lines.For comparison, light beam paths 13 emitted from a point 14 located on the optical axis 3 are also shown as gray lines. The light emitted from point 14 on the sample is converted into a collimated light beam by the focusing element 6 and guided through the multimode optical fiber 2. In order to be converted into a collimated light beam by the focusing element 6, point 14 on the sample must be in a focal plane of the focusing element 6. The collimated light beam then has an angle to the optical axis 3 of the multimode optical fiber 2 that depends on the distance of point 14 from the optical axis 3. The greater the distance of point 14 from the optical axis 3, the greater the angle of the collimated light beam to the optical axis 3.An axial component of the light's k-vector is a propagation constant, meaning that the axial component of the k-vector is maintained from the point of entry into the multimode optical fiber 2 until exiting the multimode optical fiber 2. This is particularly pronounced in step-index fibers. Since the axial component of the k-vector is related to the angle of the light to the optical axis 3, light entering the multimode optical fiber 2 at a specific angle to the optical axis 3 of the multimode optical fiber 2 exits the multimode optical fiber 2 as a light cone, with the aperture angle of the light cone to the optical axis 3 being equal to the specific angle, which in turn depends on the distance of the point 14 of the sample emitting the light from the optical axis 3.If only the light emerging at the predetermined angle to the optical axis 3 is detected by the detector unit 12, then only light from points 14 that are at the same distance from the optical axis 3 as the point 14 of the sample to be observed is detected. The light from points 14 that are at a different distance from the optical axis 3 is not detected. This selective detection results in a high contrast of the endoscopic detector system 11. The same applies if only the light emerging at several predetermined angles to the optical axis 3 is detected by the detector unit 12. Then only light from points 14 that are at the same distance from the optical axis 3 as several points 14 of the sample to be observed is detected.If these multiple points 14 are sufficiently far apart from each other and have different distances from the optical axis 3, a high contrast of the endoscopic detector system 11 is also achieved and by simultaneously examining multiple points 14 the total examination time can be shortened.
[0074] In the present embodiment, the detector unit 12 comprises a detector arrangement 15 configured to selectively detect light in one or more annular regions. The detector arrangement 15 comprises a selection element 16 embodied as an annular aperture for selecting the one or more annular regions. The detector arrangement 15 further comprises a detector element 17 for detecting the light arriving in the selected one or more annular regions. The annular aperture can be adapted to different radii of the annular regions; for example, different annular apertures with different radii can be interchangeable. In this case, the detector element 17 is arranged on the side of the selection element 16 facing away from the proximal end 4 of the multimode optical fiber 2, so that light transmitted through the aperture strikes the detector 17 and is registered by it.Alternatively, the selection element 16 can be an annular mirror that only reflects light arriving in an annular region. The detector 17 is then arranged on the same side of the selection element 16 as the proximal end 4 of the multimode optical fiber 2. A variable annular mirror can be implemented, for example, as a micromirror array.
[0075] Figure 4 shows a schematic longitudinal section through a further embodiment of an endoscopic detector system 11. Compared to the embodiment shown in Figure 3, the detector unit 12 of this endoscopic detector system 11 further comprises a further focusing element 18 facing the proximal end 4. This further focusing element 18 is shown as a lens. The further focusing element 18 focuses the light emerging from the multimode optical fiber 2 at one or more predetermined angles onto one or more annular regions in a focal plane of the further focusing element 18, where the selection element 16 is also arranged. This further increases the angular resolution of the detector unit 12.
[0076] Figure 5 shows a schematic longitudinal section through yet another embodiment of an endoscopic detector system 11. In comparison to the embodiment shown in Figure 4, the detector arrangement 15 of this endoscopic detector system 11 does not comprise a selection element 16. Instead, the detector element 17 is designed to selectively detect light in the one or more annular regions. The detector element 17 can, for example, have annular detector regions. Alternatively, the detector element 17 can comprise a grid arrangement with individual pixels arranged in rows and columns, in which case only the pixels that lie on an annular region with a predetermined radius are evaluated for selectively detecting the light. This allows various annular regions to be examined quickly and easily.
[0077] Figure 6 shows a schematic longitudinal section through an embodiment of an endoscopic system 19. The endoscopic system 19 comprises the endoscopic detector system 11 according to one of the embodiments described above, as well as an illumination device 20, which here comprises a coherent light source 21, for example, a laser. The illumination device 20 is designed to illuminate a sample 22 or a portion of a sample. This sample 22 can be an inorganic or an organic sample, for example, an animal or a human.
[0078] In the present embodiment, the illumination device 20 is designed to illuminate a light sheet 23. This light sheet 23 extends, in particular, perpendicular to the optical axis 3 and intersects the sample 22. The fluorescence emitted by the sample 22 is then detected by the endoscopic detector system 11. Using a transfer matrix of the optical fiber arrangement 1, the light detected by the endoscopic detector system 11 can then be used to infer light points 14 in the sample 22. This is an inverse problem that can be solved, for example, using the maximum likelihood method. Since the present detector system 11 can selectively detect points 14 in the sample 22 that are located on annular regions in the sample 22, the contrast of the resulting image is improved. Figure 7 shows a schematic longitudinal section through another embodiment of an endoscopic system 19.Compared to the endoscopic system 19 of the exemplary embodiment shown in Figure 6, the illumination device 20 comprises, in addition to the coherent light source 21, a light modulator 24 and a semi-transparent mirror 25. The coherent light source 21 is, in particular, a laser. The coherent light source 21 and the light modulator 24 are configured such that the coherent light source 21 emits coherent light, which is then pre-shaped by the light modulator 24 and fed via the semi-transparent mirror 25 into the proximal end 4 of the multimode optical fiber 2. The light modulation can be carried out, in particular, as amplitude, phase, and / or polarization modulation. The light modulation is carried out, in particular, such that one point 14 or a few points 14 of the sample 22 are illuminated.Thus, only this point or these points 14 in the sample 22 are illuminated, and stray light is suppressed by the endoscopic detector system 11, achieving particularly good contrast and thus particularly good image quality. If a few points 14 in the sample 22 are illuminated, these points 14 are at different distances from the optical axis 3, so that the light emitted by these points 14 enters the multimode optical fiber 2 at different angles and exits the multimode optical fiber 2 at correspondingly different angles, where it can then be differentiated by the detector unit 12. This enables the simultaneous illumination of several points 14, enabling faster endoscopic image acquisition.The light modulation required to illuminate a specific point 14 can be determined, for example, by determining a transmission matrix that describes the transfer of coherent light from one end of the optical fiber array 1 to the other side of the optical fiber array 1. This can be achieved, for example, by determining the light transfer from a plurality of known points that emit coherent light. Using the transmission matrix, the modulation of the coherent light required to illuminate one or a few points 14 in the sample 22 is then determined. Figure 8 shows a schematic longitudinal section through yet another embodiment of an endoscopic system 19. This endoscopic system 19 comprises an illumination device 20 and an optical fiber array 1.
[0079] The illumination device 20 comprises a pulsed light source 21, in particular a pulsed coherent light source, most particularly a pulsed laser. Furthermore, the illumination device 20 comprises a light modulator 24 configured such that the pulsed light is fed into the proximal end 4 of the multimode optical fiber 2 at at least one predetermined angle to the optical axis 3. Since light fed into the multimode optical fiber 2 at a specific angle propagates primarily within a mode group, with one mode group comprising modes exhibiting a similar propagation velocity, little or no intermodal dispersion occurs, so that the light pulse is preserved.If the light is applied at more than one predetermined angle, the light pulses for the respective angles are retained, and multiple points 14 of the sample 22, which are at different distances from the optical axis 3, can be illuminated simultaneously. Furthermore, if the multimode optical fiber 2 is a step-index fiber, a circular polarization state of the coherent light is also retained. Other microscopy techniques, such as fluorescence lifetime microscopy, STED (stimulated emission depletion) microscopy, or multiphoton microscopy, also benefit from the improved light pulses obtained in this way.
[0080] In addition to the light modulator 24, the lighting device 20 may also have lenses 26 and / or apertures.
[0081] For example, a further optical system with a detector can be provided to detect the light emitted by the sample 22 by fluorescence.
[0082] Figure 9 shows a schematic longitudinal section through yet another embodiment of an endoscopic system 19. In addition to the endoscopic system 19 shown in Figure 8, this endoscopic system 19 comprises a semi-transparent mirror 25 and a detector 17. The detector 17 detects light emitted by the sample 22 by fluorescence, entering the multimode optical fiber 2 at the distal end 5 via the focusing element 6, guided by the multimode optical fiber 2, exiting the multimode optical fiber 2 at the proximal end 4, and deflected by the semi-transparent mirror 25. Examples of such a detector 17 are a photodetector, a camera, a photon counter, in particular a photomultiplier, a hybrid photodetector, and a single-photon avalanche diode.
Claims
Claims 1. An endoscopic detector system (11) comprising an optical fiber arrangement (1) comprising a multimode optical fiber (2) having an optical axis (3), a proximal end (4), and a distal end (5); and a focusing element (6) arranged at the distal end (5) of the multimode optical fiber (2); and a detector unit (12) arranged at the proximal end (4) of the multimode optical fiber (2), which detector unit is designed to separately detect light emerging from the multimode optical fiber (2) at the proximal end (4) at one or more predetermined angles to the optical axis (3).
2. The endoscopic detector system (11) according to claim 1, wherein the optical fiber arrangement (1) further comprises a light reflection surface (9) arranged at the distal end (5) of the multimode optical fiber (2) and / or at the focusing element (6), wherein an angle between the normal to the light reflection surface (9) and the optical axis (3) of the multimode optical fiber (2) at the distal end (5) is between 30° and 60°, in particular between 40° and 50°.
3. The endoscopic detector system (11) according to claim 1 or 2, wherein the focusing element (6) is a gradient index lens (6) which is connected in particular to the multimode optical fiber (2) to form a composite optical fiber (1).
4. The endoscopic detector system (11) according to claim 1 or 2, wherein the focusing element (6) is a spherical lens, a plano-convex lens, or a Fresnel lens.
5. The endoscopic detector system (11) according to any one of claims 1 to 4, wherein the detector unit (12) comprises a detector array (15) configured to selectively detect light in one or more annular regions corresponding to the one or more predetermined angles.
6. The endoscopic detector system (11) according to claim 5, wherein the detector unit (12) further comprises a further focusing element (18) facing the proximal end (4) of the multimode optical fiber (2).
7. The endoscopic detector system (11) according to claim 5 or 6, wherein the detector arrangement (15) comprises: a selection element (16), arranged in particular at the focus of the further focusing element (18), for selecting the one or more annular regions; and a detector element (17) for detecting the light arriving in the selected one or more annular regions.
8. The endoscopic detector system (11) according to claim 5 or 6, wherein the detector arrangement (15) comprises a detector element (17), arranged in particular in the focus of the further focusing element (18), which is designed to selectively detect light in the one or more annular regions.
9. A composite optical fiber (1) comprising a multimode optical fiber (2) having an optical axis (3), a proximal end (4), and a distal end (5); and a gradient index lens (6) connected to the distal end (5) of the multimode optical fiber (2).
10. The composite optical fiber (1) according to claim 9, wherein the gradient index lens (6) has a light reflection surface (9), wherein an angle between the normal to the light reflection surface (9) and the optical axis (3) of the multimode optical fiber (2) at the distal end (5) is between 30° and 60°, in particular between 40° and 50°.
11. An endoscopic system (19) comprising an illumination device (20) and the endoscopic detector system (11) according to one of claims 1 to 8.
12. The endoscopic system (19) according to claim 11, wherein the illumination device (20) is designed to illuminate a light sheet (23).
13. The endoscopic system (19) according to claim 11, wherein the illumination device (20) comprises a coherent light source (21) and a light modulator (24) configured such that the coherent light source (21) emits coherent light which is pre-shaped by the light modulator (24) and fed into the proximal end (4) of the multimode optical fiber (2).
14. An endoscopic system (19) comprising an illumination device (20) comprising a pulsed coherent light source (21) and a light modulator (24), and an optical fiber arrangement (1) comprising a multimode optical fiber (2) having an optical axis (3), a proximal end (4) and a distal end (5), and a focusing element (6) arranged at the distal end (5) of the multimode optical fiber (2), wherein the light modulator (24) is configured such that the pulsed coherent light is fed into the proximal end (4) of the multimode optical fiber (2) at at least one predetermined angle to the optical axis (3).
15. A method for examining a sample (22) using an endoscopic system (19) according to one of claims 11 to 14, comprising: Illuminating the sample (22) by means of the illumination device (20); and Detecting the light entering the distal end (5) of the multimode optical fiber (2), guided by the multimode optical fiber (2) and exiting the proximal end (4) of the multimode optical fiber (2) at one or more predetermined angles to the optical axis (3).
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