Optical device for multi-modal microscopy
The optical device with integrated meta-lenses and longpass filters addresses the bulkiness and alignment issues of conventional microscopes, providing a compact, cost-effective solution for multi-modal imaging with high resolution and versatility.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2025-09-01
- Publication Date
- 2026-03-05
AI Technical Summary
Conventional fluorescence microscopes are bulky, costly, and require meticulous alignment of complex optical components, limiting their usability and scalability.
An optical device comprising a transparent base substrate with integrated light modulating and longpass filter layers, featuring an array of meta-lenses and a longpass filter with a specific cut-on wavelength, enabling compact, multi-modal imaging without the need for mechanical scanning or complex alignment.
Enables high-resolution imaging over a large field of view in a miniaturized form factor, supporting multiple imaging modalities like fluorescence, brightfield, and digital holography, while reducing manufacturing costs and complexity.
Smart Images

Figure EP2025074827_05032026_PF_FP_ABST
Abstract
Description
[0001] Optical device for multi-modal microscopy
[0002] Field of the invention
[0003] The present invention relates to the field of optical microscopy, and more specifically to optical devices and articles for use in a multi-modal optical microscope.
[0004] Background of the invention
[0005] Fluorescence microscopy is an imaging technique that uses fluorescence light to observe and study samples. It is widely used in life science, including various biological disciplines such as cell biology, histology, and point-of-care diagnostics. Samples of interest must be labeled with fluorescent dyes to visualize them with sufficient contrast in a fluorescence microscope. This enables the detection, visualization, and quantification of biological parameters. Fluorescence microscopy is also commonly employed to monitor the progression of bioassays or determine an end-point status, such as the presence of an analyte or molecule.
[0006] In a fluorescent light microscope, the samples are irradiated with excitation light. Each dye molecule within an irradiated sample absorbs photons of the excitation light and emits fluorescence photons. Due to the spectral Stokes shift in fluorescence, separating the fluorescence from the excitation light is necessary before photon detection. Wavelength-selective optical components like filters and beam splitters can be used to separate the excitation light from the fluorescent light. Typical fluorescent light microscopes rely on high numerical aperture (NA) lenses to efficiently collect the emitted fluorescence photons before filtering the excitation light. Sensitive point photodetectors such as photomultiplier tubes or avalanche photodiodes can be used to detect the fluorescent photons in the image plane. A scanning process is often required to create 2D or 3D representations of objects inside a sample.
[0007] Conventional benchtop microscopy systems are standalone units that contain sophisticated optical trains including many highly specialized bulk optical components. These must be aligned meticulously at the component level. This results in bulkiness, large costs, and makes the operation of conventional microscopy systems more difficult.
[0008] Despite the advancements in fluorescence microscopy and the development of alternative imaging techniques, there is still a need for further improvements which address the challenges faced by conventional imaging and detection systems.
[0009] Summary of the invention
[0010] It is an object of embodiments of the present invention to overcome the above-mentioned shortcomings.
[0011] The above objective is accomplished by an optical microscope article, a multi-modal optical microscope comprising and multi-modal microscopy techniques using this article as set out in the claims of the present invention.
[0012] In one aspect, the invention relates to an optical microscope article which comprises an optically transparent base substrate, a light modulating layer integrated with the base substrate, and a longpass filter layer in optical communication with one of a light-receiving front face and a light-transmitting rear face of the light modulating layer. The light modulating layer, disposed at a first position along a longitudinal axis of the article, comprises an array of micro- or nanostructured unit cells. Each unit cell includes a transmissive meta-lens configured to image objects located at a distance from the light-receiving front face of the light modulating layer at a corresponding distance from the light-transmitting rear face of the light modulating layer. The longpass filter layer, disposed a second position along said longitudinal axis, has a filter edge with a distinctive cut-on wavelength. A modulation band of the light modulating layer designates the operational wavelength range throughout which the individual meta-lenses of the light modulating layer achieve the imaging of objects placed at said distance from the light-receiving front face. The modulation band has a distinctive cut-on wavelength that is smaller than or equal to the cut-on wavelength of the longpass filter layer.
[0013] It is an advantage of embodiments of the invention to provide an optical device that enables multi-modal microscopic imaging in a compact form factor, is easy to use and replace, and does not need regular and lengthy optical alignment of its components.
[0014] It is a further advantage of embodiment of the invention that a large field of view can be obtained at good resolution without requiring mechanical scanning.
[0015] In embodiments of the invention, the distance from the light-receiving front face typically denotes the object distance and the corresponding distance from the light-transmitting rear face of the light modulating layer typically denotes the image distance. Objects at various distances from the light-receiving front face of the light modulating layer can be imaged at corresponding distances from the rear face of the light modulating layer, provided that objects are located farther away from the light-receiving front face than a predetermined minimum distance. The shortest effective focal length associated with the meta-lenses of the light modulating layer may correspond to the predetermined minimum distance. In embodiments of the invention, the object distance and corresponding distance from the light-transmitting rear face of the light modulating layer can be as large as 100 mm - allowing imaging of objects with sufficient distance in the sample due to application-specific needs - but more preferably are about 10 mm or less to facilitate an enhanced sensitivity of the light gathering capability of the meta-lenses, in addition to the benefits of compactness. The object distances and the corresponding distances from the light-receiving front face can be directly correlated as in the paraxial imaging condition of a thin lens. Alternatively, it is possible to decouple the distance relationship in more complex designs, similar to the case of multielement lens design. Nevertheless, the conjugate plane relation defined by the object and imaging distances generally continues to apply.
[0016] In embodiments, the light modulating layer may be formed on a face of the base substrate, or the light modulating layer may comprise a patterned surface portion of the base substrate. This allows for compact and repeatable integration and flat optical devices.
[0017] In embodiments, the base substrate may be an optical flat. This provides a high-quality optical surface and reduces or removes imaging artifacts and stray light influence.
[0018] In embodiments, the optical device may further comprise a color filter layer disposed at a third position along the longitudinal axis, the color filter comprising at least one filter passband falling into the modulation band of the light modulating layer. The color filter may be an emission filter. This enables source or excitation light removal before detecting imaged fluorescent light. Furthermore, the color filter layer may comprise multiple different filter passbands at corresponding different positions within the color filter layer, whereby different unit cells of the light modulating layer may be associated with different filter passbands of the color filter layer. This allows for simultaneous multi-color imaging such as multi-color fluorescent microcopy.
[0019] In embodiments, unit cells of the light modulating layer may be separated by light blocking regions. This advantageously reduces the fraction of non-modulated light leaving the light modulating layer, thus increasing the light modulation efficiency of the light modulating layer. Undesirable light leakage between the unit cells can be prevented.
[0020] In embodiments, each unit cell of the light modulating layer may be further configured to transmit incident light at one or more wavelengths outside the modulation band , without focusing light emanating from points on objects located at a distance from a light-receiving front face of the light modulating layer into respective spots at a corresponding distance from a light-transmitting rear face of the light modulating layer. In other words, each unit cell ceases to be working as a meta-lens if operated at said one or more wavelengths outside the modulation band, e.g. if operated at longer wavelength beyond the modulation band. The meta-lenses within each unit cell can be designed to lose their light-focusing properties or exhibit weaker light convergence properties for incident light that falls outside the modulation band, which means that images of distant objects are no longer formed at the corresponding distance from the rear face of the light modulating layer. Instead, light emanating from points on the object that is incident on the light-receiving front face of the light modulating layer is spread out over an area portion significantly larger than a focal spot size associated with each unit cell when reaching a detector or image plane, e.g. positioned at the image distance from the rear face of the light modulating layer. This has the advantage that additional imaging modes that do not rely on lens-based image formation, such as lens-free digital inline holography, can be selected based on an illumination wavelength range.
[0021] For instance, each unit cell may be designed as a chromatically corrected meta-lens within the modulation band but exhibit a strongly diverging focal length, e.g. larger or smaller effective focal length compared to the achromatic focal range, when operated outside the modulation band. A relative change in the effective focal length associated with each unit cell of the light modulating layer may be at least 10%.
[0022] In embodiments, the arrayed unit cells of the light modulating layer may be organized into one-dimensional, e.g. line array, or two-dimensional arrays, e.g. tiled in accordance with a 2D grid. This provides design flexibility.
[0023] In embodiments, the base substrate, the light modulating layer and the longpass filter layer may form a vertical multilayer stack. This enables a compact, lightweight, robust and flat device. In embodiments, the optical article may be an integrated optics device. This has the advantage of offering low-cost, ultra-thin, lightweight, mass-manufacturable optical articles, in which the alignment conditions for its functionally different optical components are met with good accuracy during manufacture. An initial alignment and periodic realignment are no longer necessary. Moreover, thermal and vibration effects may be less pronounced for flat integrated optical devices compared to bulk optical trains. In embodiments, the optics device may have a device thickness T along the longitudinal axis and a device width W along a transverse axis, perpendicular to the longitudinal axis, wherein the thickness to width ratio is T:W < 1 ,0.
[0024] In embodiments, the optics device may further comprise an actuator for switching on and off the imaging of objects by the meta-lenses of the light modulating layer. This allows for dynamic control of the lens-based imaging properties of the unit cells in the light modulating layer, e.g. provide an alternative means for selecting an imaging modality in addition to illumination wavelength. In embodiments, the light modulating properties may be switched on an off for each unit cell individually, for groups of unit cells, e.g. different rows, columns, radii, etc., or for all unit cells of the array in unison.
[0025] In embodiments, a focal length associated with each unit cell of the light modulating layer, when operated as a meta-lens, may vary as a function of wavelength, the variation of said focal length being less than 100 pm across the modulation band. This provides good achromatic performance.
[0026] In embodiments, the longpass filter layer may be formed on the base substrate. This allows for integrated fabrication and less post-processing steps. In embodiments, the longpass filter layer may be applied directly to the light modulating layer. This beneficially minimizes the device’s thickness.
[0027] In embodiments, the longpass filter layer and the light modulating layer may be formed on opposite faces of the base substrate. This provides flexibility in the layer ordering. Moreover, the use of the same substrate for the longpass filter layer and the light modulating layer reduces material costs as well as the weight and thickness of the optical device.
[0028] In embodiments of the invention, a common base substrate for the longpass filter layer and the light modulating layer may be made of glass or polymer material. A common material system, such as dielectrics including, e.g., stacked thin film dielectrics, may be used for the manufacture of the longpass filter layer and the light modulating layer by commercially available tools. Formation of the longpass filter layer and the light modulating layer may be achieved by mass manufacturing methods, including, e.g., material deposition, patterning, and etching. This has the advantage that the longpass filter layer and the light modulating layer can be reliably integrated with the base substrate during or following their manufacture, thereby reducing the optical device cost while increasing the optical device compactness and yield.
[0029] In embodiments, the longpass filter layer, the light modulating layer and optional color filter layers may be formed in CMOS-compatible materials. This enables accurate, scalable and mass- producible optical articles.
[0030] In alternative embodiments, the longpass filter layer may be formed on a filter substrate distinct from the base substrate, the filter substrate and the base substrate being stacked along a longitudinal axis of the optical device. This allows using different substrates optimized for each layer during device fabrication. In embodiments, the filter substrate and the base substrate may be spaced apart from each other by a filler medium and / or one or multiple spacing elements. This allows for precise control of the layer spacing between the different functional optical layers. In some embodiments, a bonding layer may join the filter substrate to the base substrate. This provides mechanical stability.
[0031] In embodiments, a transparency range of the base substrate may comprise wavelengths between 200 nm and 900 nm and / or wavelengths between 900 nm and 2500 nm. This covers the visible and near-infrared spectrum which are commonly used in microscopy applications.
[0032] In embodiments, each meta-lens of the light modulating layer may comprise or be formed of a geometrical arrangement of a plurality of micro- or nanostructured optical elements, e.g. up to millions or billions of micro- or nanostructured optical elements, typically smaller than the wavelength of light. These sub-wavelength structures, often referred to as “meta-atoms”, resonantly couple to the electric and magnetic fields of the incident light beams. Specifically, the meta-atom pattern modifies the phase profile of the incident light beam, causing the beam to be bent. These meta-atoms are tiny, nanoscale structures with varying shapes and sizes whose position across the lens can be arbitrary and are designed to control the interaction of light. By carefully designing the size, shape, and arrangement of these meta-atoms, the meta-lens can control how the incident light interacts with it. This enables engineering the optical response of the meta-lens within each unit cell, including focal length, achromaticity / spectral response, resolution, absorption curve, reflection curve, polarization response, etc. The micro- or nanostructured optical elements composing the meta-lens of each unit cell of the light modulating layer may be selected from the following list: optical antennas, plasmonic structures, posts, rings, fins, ribs, ribbons, arcs, holes, slits. These are suitable building blocks for meta-lenses. The relative size or lateral dimension of the optical elements may be varied across each metasurface. Moreover, the density of the optical elements may be adjusted locally on each metasurface, e.g. to obtain more efficient light convergence properties of the different unit cells. The micro- or nanostructured optical elements may be metallic structures, dielectric structures, or combinations of both. Optical elements of different heights, sizes or shapes may be combined in an element group, e.g. optical dimers, which are used as a building block when building the meta-lens. It is preferable to have optical elements formed of a high refractive index material relative to the interstitial material or medium that extends between the individual elements, i.e., each unit cell comprises at least two refractive index mismatched materials. A high refractive index contrast is desirable since this leads to stronger and more efficient scattering and / or diffraction by the individual micro- or nanostructured optical elements. This in turn improves the compactness of the optical device.
[0033] In embodiments, the modulation band may comprise wavelength in the range from 500 nm to 700 nm, e.g. between 450 nm and 500 nm, and / or a spectral bandwidth of the modulation band may be at least 50 nm. This is suitable for most fluorescence microscopy applications. In embodiments, the predetermined modulation band may exclude wavelengths above 700 nm. This enables the use of the optical device for digital inline holographic microscopy in the near-infrared and avoids crosstalk with near-infrared fluorescent markers. In embodiments, a lateral dimension of each unit cell of the light modulating layer may be at most 1 ,0 cm. This enables high resolution imaging over a large field of view, especially if many such unit cells are tiled into an even bigger array. In embodiments, each unit cell of the light modulating layer may have a thickness, t, along the longitudinal axis of the optical device, said thickness being 1 ,0 mm at most, preferably t < 100 pm, e.g. t < 10 pm. This enables flat, quasi-2D devices with reduced bulk optical effects. In embodiments, the array of unit cells of the light modulating layer may span an area of size A, such that the thickness to surface area ratio is t:A > 1000 mm1.
[0034] In some embodiments, each unit cell of the light modulating layer may comprise a plurality of meta-lenses, stacked along the longitudinal axis. This enables extended achromatic working ranges / modulation bands and / or the improved correction of optical aberrations.
[0035] In embodiments, the meta-lenses of the different unit cells may be formed on a planar or slightly curved surface. The meta-lenses of the different unit cells may be coplanar with each other, e.g. formed on the same plane or planar surface of the base substrate. This simplifies fabrication. In some specific embodiments of the invention, this plane may be angled with an opposite outer surface of the base substrate. This allows for use of the optical devices in microscopes in which an image detector or image sensor is positioned at an angle with respect to the longitudinal axis of the optical device.
[0036] In embodiments, the optical device may comprise at least one further light modulating layer such as a second light-modulating layer formed on an opposite face of the base substrate. This enables more complex optical functions such as independently tailoring amplitude and phase response of the light-modulating layers, or independently tailoring phase and polarization response of the light-modulating layers.
[0037] In another aspect, the present invention relates to an optical device for use in an optical microscope. The optical device comprises an optically transparent base substrate, a light modulating layer integrated with the base substrate and disposed at a first position along a longitudinal axis of the optical device, and a longpass filter layer in optical communication with one of a front face and a rear face of the light modulating layer and disposed a second position along said longitudinal axis. The light modulating layer comprises an array of unit cells. Each unit cell is configured as or configured to act as a transmissive meta-lens suitable for individually imaging objects located at a distance from the light-receiving front face at a corresponding distance from the light-transmitting rear face of the light modulating layer. Each unit cell of the light modulating layer acts as a meta-lens with respect to wavelengths falling in an operational wavelength range, referred to as modulation band of the light modulating layer, which may be defined as the wavelength range in which an axial focus shift for the unit cell is limited to 100 pm. The modulation band has a distinctive cut-on wavelength that is smaller compared to distinctive cut-on wavelength associated with a filter edge of the longpass filter layer.
[0038] Each meta-lens of the light modulating layer typically comprises a plurality of micro- or nanostructured optical elements which are geometrically arranged on a two-dimensional surface to form a meta-surface lens. That is, a two-dimensional pattern of micro- or nanostructures comprised by each unit cell has the imaging properties of a lens.
[0039] In a further aspect, the present invention relates an optical microscope that is selectively operable as a brightfield microscope and a fluorescent light microscope. The optical microscope comprising the optical device according to embodiments of any one of the previous aspects, and an illumination unit arranged to irradiate objects to be imaged with source light. An emission wavelength range for the source light is selectable between a first emission range, associated with excitation light, and a second emission range, associated with brightfield light, when operating the optical microscope as fluorescent light microscope and brightfield microscope, respectively. The first emission range and the second emission range are non-overlapping wavelength ranges, wherein the second emission range is comprised by the modulation band of the light modulating layer of the optical device. The cut-on wavelength of the longpass filter layer of the optical device is situated between the first emission range and the second emission range, whereby the longpass filter blocks source light in the first emission range but transmits source light in the second emission range.
[0040] In embodiments, the optical microscope further comprises an image detector / sensor in optical communication with the rear face of the light modulating layer of the optical device. A photosensitive layer of the image detector / sensor may comprise a plurality of photodetectors, the photosensitive layer being integrated with the base substrate of the optics device. This enables a more compact optical microscope.
[0041] In embodiments, the image sensor and the light modulating layer of the optical device may be separated by an imaging distance. This imaging distance may be adjustable. This allows for adjustable magnification of the optical microscope. Moreover, the upper and lower wavelength limit of the modulation band of the optical device may be a function of the imaging distance, whereas an optical bandwidth associated with the modulation band is independent of the imaging distance. This has the benefit of allowing the tuning of a spectral position of the modulation band within tuning ranges of the optical microscope. However, one or more wavelengths or spectral regions outside the modulation band and its tuning ranges may be transmitted by each unit cell without acting as a meta-lens. This means that at these remote wavelengths or spectral regions, the light modulating layer transmits the incident light but loses its focusing or light convergence properties. In consequence, light at these remote wavelengths or spectral regions that is emanating from distant object points will no longer be imaged to corresponding points at a distance from the rear face of the light modulating layer but spread out over an area portion substantially larger than a focal spot size associated with each unit cell operated with incident light within the modulation band. This enables digital holographic microscopy as an additional imaging mode.
[0042] In embodiments, the imaging distance may be equal to a focal length associated with the meta-lenses of the light modulating layer. This maximizes the light collection efficiency. In other embodiments, the imaging distance may be larger than focal length associated with the meta-lenses of the light modulating layer, e.g., imaging distances up to 5f (f: focal length) are possible. The imaging distance may range between 100 mm and 100 pm, with distances smaller than 10 mm being preferred for light efficiency reasons.
[0043] In embodiments, the illumination unit may comprise multiple light emitters configured to deliver source light in the second emission range at various illumination angles, and / or the illumination unit may be configured to irradiate the objects to be imaged from various illumination angles. This enables contrast enhancement techniques such as brightfield imaging with Fourier ptychography as an additional imaging mode. Additionally, the illumination unit may be configured to deliver source light in the second emission range at various wavelengths. Illuminating objects to be imaged at different wavelengths within the second emission range has the advantage of enabling noise reduction through phase-retrieval methods in the brightfield mode.
[0044] In embodiments, the illumination unit may be arranged to irradiate the objects to be imaged with a collimated beam of source light selected from a third emission range beyond the predetermined modulation band of the light modulating layer of the optics device, thus operating as a holographic microscope. This enables digital holographic microscopy as an additional imaging mode.
[0045] In yet another aspect, the invention relates to multi-modal microscopy method which uses the optical device according to embodiments of any of previous aspects. The method comprises: providing an optical microscope including optical device according to embodiments of any one of previous aspects, operating the optical microscope in a fluorescence microscopy mode, by selecting excitation light used to illuminate objects of interest in the fluorescence microscopy mode to have shorter wavelengths than the cut-on wavelength of the longpass filter layer of the optical device, operating the optical microscope in a brightfield microscopy mode, by selecting brightfield light used to illuminate objects of interest in the brightfield microscopy mode to have wavelengths longer than the cut-on wavelength of the longpass filter layer and falling into the modulation band of the light modulating layer of the optical device.
[0046] Optionally, raw images recorded by the optical microscope may be subjected to a postprocessing step to enhance image quality. The post-processing step may include an image calibration step, e.g. by applying image calibration rules in accordance with calibration files, and / or the application of one or multiple physics-based algorithms such as Fourier transforms, deconvolution or optical wave propagation, which account for the optical unit impulse response of the optical microscope. The post-processing step may be carried out by a processing unit external or internal to the image sensor hardware of the optical microscope, e.g. by running a software component on the processing unit that comprises corresponding machine-interpretable instructions.
[0047] In embodiments, the multi-modal microscopy method may further include operating the optical microscope in a digital holographic microscopy mode, by selecting reference light used to illuminate objects of interest in the digital holographic microscopy mode to have wavelengths beyond the modulation band of the light modulating layer of the optical device. This enables an additional label-free quantitative phase imaging mode. It is an advantage of embodiments of the present invention that a compact, integrated optical device for multi-modal microscopy can be achieved. It is a further advantage of embodiments of the present invention that the optics device enables selective operation of an optical microscope in a brightfield microscopy mode and a fluorescence microscopy mode without requiring moving parts. It is still another advantage of embodiments of the present invention that the optics device enables a digital holographic microscopy mode in addition to the brightfield and fluorescence microscopy modes.
[0048] It is an additional advantage of embodiments of the present invention that high resolution imaging over a large field of view can be realized in a miniaturized microscope system. Another advantage of embodiments of the present invention relies on the fact that the optical device can be manufactured in a cost-effective manner using established semiconductor fabrication techniques.
[0049] In yet another aspect, the invention relates to an optical microscope that is selectively operable as a brightfield microscope and a fluorescent light microscope. The optical microscope comprising a means for receiving and securing the optical device according to embodiments of any one of the previous aspects, an image sensor, and an illumination unit arranged to irradiate objects to be imaged with source light. An emission wavelength range for the source light is selectable between a first emission range, associated with excitation light, and a second emission range, associated with brightfield light, when operating the optical microscope as fluorescent light microscope and brightfield microscope, respectively. The first emission range and the second emission range are non-overlapping wavelength ranges, wherein the second emission range is comprised by the modulation band of the light modulating layer of the optical device. The cut-on wavelength of the longpass filter layer of the optical device is situated between the first emission range and the second emission range, whereby the longpass filter blocks source light in the first emission range from reaching the image sensor but transmits source light in the second emission range. The image sensor is in optical communication with the rear face of the light modulating layer of the optical device when the optical device is secured in the optical microscope.
[0050] In embodiments, the receiving means may be a device holder which secures the optical device in a position where the image sensor is in optical communication with the rear face of the light modulating layer of the optical device. The device holder may be configured to releasably receive the optical device. The device holder may be specifically adapted to receive and secure optical devices with a predetermined shape and dimensions such as replaceable cartridge-like optical devices. The device holder may be configured to position and secure optical devices accurately and repeatedly relative to the illumination unit and / or the image sensor. The device holder may comprise one or more of the following components: a clamp structure, a receiving slot, guides or guiding rails, a positioning pin, a recess structure, a suction means, a stopping means. The device holder of the optical microscope and the optical device interact to receive, position and secure the optical device in the optical microscope with respect to the illumination unit and the image sensor, thus enabling multi-modal microscopy. The optical microscope and the optical device may be complementary parts of a multi-modal microscopy system. Particular and preferred aspects of the invention are set out in the accompanying independent and dependent claims. Features from the dependent claims may be combined with features of the independent claims and with features of other dependent claims as appropriate and not merely as explicitly set out in the claims.
[0051] For purposes of summarizing the invention and the advantages achieved over the prior art, certain objects and advantages of the invention have been described herein above. Of course, it is to be understood that not necessarily all such objects or advantages may be achieved in accordance with any particular embodiment of the invention. Thus, for example, those skilled in the art will recognize that the invention may be embodied or carried out in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other objects or advantages as may be taught or suggested herein.
[0052] The above and other aspects of the invention will be apparent from and elucidated with reference to the embodiment(s) described hereinafter.
[0053] Brief description of the drawings
[0054] The invention will now be described further, by way of example, with reference to the accompanying drawings, in which:
[0055] FIG. 1 and FIG. 2 are cross-sectional views of an optical microscope article according to a first embodiment.
[0056] FIG. 3 shows the spectral response curves of the light modulating layer and the longpass filter layer in optical articles in accordance with embodiments of the invention.
[0057] FIG. 4 illustrates arrayed arrangements of unit cells of the light modulating layer in accordance with embodiments of the invention.
[0058] FIG. 5 is a cross-sectional view of an optical article according to a second embodiment.
[0059] FIG. 6 is a cross-sectional view of an optical article according to a third embodiment.
[0060] FIG. 7 is a cross-sectional view of an optical article according to a third embodiment.
[0061] FIG. 8 is a cross-sectional view of an optical article according to a fourth embodiment.
[0062] FIG. 9 is a cross-sectional view of an optical article according to a fifth embodiment.
[0063] FIG. 10 is a cross-sectional view of an optical article according to a sixth embodiment.
[0064] FIG. 11 to FIG. 14 illustrates different imaging modalities of an optical microscope comprising the optical article in accordance with embodiments of the invention.
[0065] The drawings are only schematic and are non-limiting. Any reference signs in the claims shall not be construed as limiting the scope.
[0066] In the different drawings, the same reference signs refer to the same or analogous elements.
[0067] Detailed description of illustrative embodiments
[0068] The present invention will be described with respect to particular embodiments and with reference to certain drawings but is only limited by the claims. It is to be noticed that the term “comprising”, used in the claims, should not be interpreted as being restricted to the means listed thereafter; it does not exclude other elements or steps. It is thus to be interpreted as specifying the presence of the stated features, integers, steps or components as referred to, but does not preclude the presence or addition of one or more other features, integers, steps or components, or groups thereof. Thus, the scope of the expression “a device comprising means A and B” should not be limited to devices consisting only of components A and B. It means that with respect to the present invention, the only relevant components of the device are A and B.
[0069] Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to one of ordinary skill in the art from this disclosure, in one or more embodiments.
[0070] Similarly, it should be appreciated that in the description of exemplary embodiments of the invention, various features of the invention are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various inventive aspects. This method of disclosure, however, is not to be interpreted as reflecting an intention that the claimed invention requires more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive aspects lie in less than all features of a single foregoing disclosed embodiment. Thus, the claims following the detailed description are hereby expressly incorporated into this detailed description, with each claim standing on its own as a separate embodiment of this invention.
[0071] Furthermore, while some embodiments described herein include some, but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention, and form different embodiments, as would be understood by those in the art.
[0072] It should be noted that the use of particular terminology when describing certain features or aspects of the invention should not be taken to imply that the terminology is being re-defined herein to be restricted to include any specific characteristics of the features or aspects of the invention with which that terminology is associated.
[0073] In the description provided herein, numerous specific details are set forth. However, it is understood that embodiments of the invention may be practiced without these specific details. In other instances, well-known methods, structures and techniques have not been shown in detail in order not to obscure an understanding of this description.
[0074] In microscopy applications, fluorescence imaging alone may not always provide sufficient information about the sample under study. It is then necessary to augment the label-based information with morphological and structural details, using complementary imaging modalities such as phase-contrast imaging, brightfield or dark-field imaging alongside fluorescence imaging. Conventional benchtop microscopy systems are standalone units that are not intended to be used in larger numbers to increase the field of view. They contain sophisticated optical trains that include many highly specialized bulk optical components, which must be aligned meticulously at the component level. This results in bulkiness, large costs, and makes the operation of conventional microscopy systems more difficult.
[0075] Lens-free microscopes have been proposed as a simpler, miniaturized and cost-effective alternative to conventional microscopy systems for the purpose of phase-contrast imaging on transparent samples or fluorescent imaging. For instance, in Jesse K. Adams et al. “Single-frame 3D fluorescence microscopy with ultraminiature lensless FlatScope”, Sci. Adv. 3, e1701548(2017), the authors describe a 3D fluorescence lens-free microscope that uses a separable 2D aperture array (amplitude mask) to achieve computational tractability of the reconstruction of fluorescence imaging scenes. However, computational complexity remains a hurdle for real-time imaging applications and imaging applications requiring a large field of view. Moreover, combining different imaging modalities within a single miniaturized lens-free microscopy system remains another major challenge.
[0076] Hereinafter, optical devices for use in an optical microscope will be disclosed, which address the challenges of combining multiple imaging modalities, reducing system complexity and cost, and enabling system miniaturization.
[0077] Hereinunder, an optical device for use in an optical microscope and an optical microscope article refer to the same object.
[0078] Embodiments of the invention are directed to an optical device for use in an optical microscope, which comprising an optically transparent base substrate, a light modulating layer integrated with the base substrate, and a longpass filter layer in optical communication with the light modulating layer. Here, the light modulating layer being integrated with the base substrate refers to the situations where the light modulating layer is monolithically formed in the base substrate, e.g. by patterning an outer surface of the base substrate, or is formed in a layer that has been permanently and firmly attached to the base substrate by deposition, bonding, or any other suitable technique. Moreover, optically transparent means that the base substrate is transmissive to light in the visible region, the near-infrared region, or both. The transparency range of the base substrate may comprise wavelengths between 200 nm and 900 nm and / or wavelengths between 900 nm and 2500 nm. The longpass filter layer in optical communication with the light modulating layer if light rays emanating from a light-transmitting face of the light modulating layer (e.g. rear face) are directed towards the longpass filter layer to be incident on and filtered by the longpass filter layer, or else if filtered light rays exiting a light-transmitting face of the longpass filter layer are directed towards and intercepted by a light-receiving face of the light modulating layer (e.g. front face). The directing of the light rays may comprise free propagation inside a transparent propagation medium, the use of optical guides or guiding (e.g. reflecting) surfaces, or combinations thereof.
[0079] A longitudinal axis of the optical device may be defined as the optical axis of the device and generally corresponds to a straight line. In embodiments of the invention, the longitudinal axis usually also coincides with a stacking direction for the base substrate, the light modulating layer and the longpass filter layer. This stacking direction also defines the thickness direction of the optical device.
[0080] In embodiments of the invention, the light modulating layer comprises an array of micro- or nanostructured unit cells. This means that each unit cell comprises a plurality of micro- or nanostructures and different such cells are arranged at different positions within the light modulating layer to form an array. The unit cells may be disposed on a planar or slightly curved outer surface of the base substrate. Preferably the different unit cells are coplanar with each other. Each unit cell may comprise a single micro- or nanostructured layer or several adjacent micro- or nanostructured layers (e.g. stacked along the thickness direction). In the former case, the micro- or nanostructures are formed on a single surface within a single material layer, while in the latter case the micro- or nanostructures are formed on two or more adjacent surfaces within the same or different material layers. Opening, spaces or gaps defined by the micro- or nanostructures may be filled by a different material including air. As suggested by the denotation, the light modulating layer has lightmodulating properties, e.g. implements one or more of a phase mask, an amplitude mask and a polarization mask, which alters the propagation of light beams impinging on each of its unit cells at the light-receiving face of the light modulating layer, by converging each light beam to a small volume, i.e. focused beam spot or image point, at a respective distance from the light-transmitting face of the light modulating layer. In general, each unit cell is configured to converge an incident beam of light, collimated or divergent, to a point at a distance of less than 10 cm from the lighttransmitting face of the light modulating layer.
[0081] Unit cells can be configured to include additional optical functions, which extend and apply to the entire light modulating layer. For example, a polarization mask or polarization modulation layer can be designed to selectively transmit a particular polarization state of light or polarization vector, while absorbing or reflecting another polarization state of light, e.g., the orthogonal polarization vector. Furthermore, the polarization mask or polarization modulation layer may include polarization-sensitive phase elements arranged to create a specific (e.g., pre-calculated) phase retardation between two orthogonal polarization components of the light beam traversing it. These additional functions allow modulating vector properties of the impinging or interacting light beams, which is useful, e.g., for polarization imaging of objects. Another example of added functionality in unit cells and the light modulation layer composed thereof can be an optical functional layer (e.g., amplitude mask, phase mask, or combination thereof) configured to apply spatially variant or invariant amplitude and / or phase changes to the light traversing the unit cell or the light modulating layer comprising many unit cells. The applied amplitude modulation may reduce the transmitted light intensity according to a pre-defined spatial profile, e.g., a circular symmetric pattern such as a Gaussian taper or inverse top-hat taper, or an asymmetric pattern such as linear ramp profile. Such amplitude modulation patterns can be used to modulate the angular spectrum of the light beam traversing the unit cells of the light modulating layer. This allows increasing or decreasing the relative support of the frequency spectrum of the light passing through each unit cell of the light modulating layer. Similarly, each unit cell of the light modulating layer may comprise spatially variant or invariant phase elements that are configured to apply relative phase shifts to the light beams traversing the light modulating layer depending on angle of incidence (e.g., differently oriented light rays impinging on the unit cells). The relative phase shifts can be confined to certain areas within the unit cell or cover the whole unit cell area. This helps create phase contrast for light beams traversing the unit cell. The above-mentioned additional functions can be implemented individually or in combination.
[0082] In embodiments of the invention, each unit cell may be configured to act as a meta-lens or include one or more meta-surfaces that have light-shaping properties, at least one of which has lens-like properties. Properties and the design of meta-surfaces, including the shaping and positioning of the plurality of micro- or nanostructures to achieve light convergence, are known in the field and described in the literature, e.g., Hu J., Bandyopadhyay S., Liu Y.-H. and Shao L.-Y.: “A Review on Metasurface: From Principle to Smart Metadevices” , Front. Phys. 8:586087, 29 January 2021 , and M. K. Chen, Y. Wu, L. Feng, Q. Fan, M. Lu, T. Xu, D. P. Tsai: “Principles, Functions, and Applications of Optical Meta-Lens” , Adv. Optical Mater, vol. 9, issue 4, 12 January 2021 , and V.-C. Su, C. H. Chu, G. Sun, and D. P. Tsai: “Advances in optical metasurfaces: fabrication and applications [Invited]”, Opt. Express, vol. 26, no. 10, p. 13148, 2018. In consequence, each unit cell of the light modulating layer can be said to include at least one transmissive meta-lens suitable for imaging distant objects, located at a distance (e.g. object) from the light-receiving front face of the light modulating layer, at a corresponding distance (e.g. imaging distance) from the light-transmitting rear face of the light modulating layer. In embodiments of the invention, each unit cell therefore has an associated effective focal length. Different unit cells may have the same or different effective focal lengths. An effective focal length of each unit cell may be 100 pm or more. Hence object points at a distance from the light-receiving face of the light modulating layer may be imaged by each unit cell individually and give rise to image points at the same or different imaging distances from the light-transmitting face, at the opposite side of the light modulating layer.
[0083] As used herein, and unless otherwise specified, the term "meta-lens" refers to a geometrical arrangement of a large collection of micro- or nanostructured optical elements. The micro- or nanostructured optical elements individually scatter and / or diffract light at wavelengths of a comparable scale but that collectively achieve light focusing or light convergence as a coherent response to light beams impinging thereon Examples of optical elements include optical antennas, plasmonic structures, posts, rings, fins, arcs, holes, and slits.
[0084] As used herein, and unless otherwise specified, the term "modulation band" refers to an operational wavelength range associated with the imaging of objects by the individual meta-lenses of the light modulating layer. Within the modulation band, the axial focal shift due to achromaticity of the meta-lenses is limited to a predetermined maximum axial focal shift, e.g. a maximum axial focal shift of 100 pm. At one or more wavelength or wavelength bands outside the modulation band and separated from the modulation band by a wavelength gap, the unit cells may no longer be operated or cease to act as meta-lenses. At these distant wavelength or wavelength bands outside the modulation band, the meta-lenses lose their light convergence properties and light beams impinging on the different unit cells are transmitted without focusing them to a spot at the imaging distance. Alternatively or additionally, the unit cells of the light modulating layer may be controlled by one or more actuators that are configured to switch on or off the light convergence properties at distant wavelength or wavelength bands outside the modulation band. For instance, actuators based on electro-optical or thermo-optical refractive index modulation may cause the micro- or nanostructures in each unit cell to lose their collective light convergence behavior. Examples of modulation bands include wavelength ranges from 450 nm to 500 nm. A spectral bandwidth of the modulation band may be at least 50 nm. Distant wavelengths outside the modulation band may be in the near-infrared spectrum, e.g. wavelengths above 700 nm.
[0085] In embodiments of the invention, a comparatively large field of view (FOV) of the light modulating layer can be synthesized from the smaller FOV’s of the individual unit cells. The FOV’s of adjacent unit cells may be partially overlapping. Moreover, the different unit cells may be configured to image different parts of an object of interest onto different image sensors, different regions of an image sensor, or a common overlap region of an image sensor. In the latter case, the unmixing of the contributions of each unit cell to a recording of the image sensor can be performed computationally by a digital processing unit, e.g. via signal separation algorithms using the unit transfer response of the light modulating layer. The overall FOV of the light modulating layer may be as large as 300 mm in diameter, while the numerical aperture (NA) of the optical device according to embodiments of the invention may exceed 0.1.
[0086] The light convergence properties of each unit cell may be combined with or complemented by the light-shaping properties of other metasurfaces, e.g. located within the same unit cell and / or in a further light modulating layer that is spaced apart from the first light modulating layer, to achieve additional phase, amplitude, polarization or chromatic responses, or to improve or correct residual aberrations of the unit cells within the first light modulating layer. Metasurfaces having the desired properties may be formed by arranging the micro- or nanostructures (e.g. pillars, towers, rods, slits, holes, antennas, plasmonic structures, etc.) in accordance with optimized geometrical patterns. Methods of obtaining, calculating and simulating such patterns in micro- or nanostructured metasurfaces are known in the art. The different unit cells of the light modulating layer may be separated by light blocking regions to avoid crosstalk between cells and stray light formation.
[0087] Examples of optical devices include devices with various configurations and / or orderings of the base substrate, light modulating layer, longpass filter layer, and optional additional layers such as color filter layers or additional light modulating layers.
[0088] In embodiments of the invention, an "optical microscope" refers to imaging or non-imaging (e.g. digital holographic) optical arrangements that include the above-described optical device in accordance with embodiments of the invention, an image sensor in optical communication with the light-transmitting face of the light modulating layer of the optical device, and an illumination unit arranged to irradiate objects of interest with source light. Examples of optical microscopes include microscopes selectively operable as a brightfield microscope and a fluorescent light microscope, microscopes with a photosensitive layer of the image sensor integrated with the base substrate of the optical device, and microscopes with an illumination unit configured to irradiate objects from various illumination angles. The optical microscope is said to be “multi-modal” if it allows selective operation between at least two different imaging modalities, such as selective operation between fluorescent imaging and brightfield imaging mode. Additional modes like Fourier ptychography or digital holographic microscopy may be selectable in some embodiments of the invention. The selectivity may be achieved through different selectable emission ranges of the illumination source and / or through actuators for switching off and on the light convergence properties of the different unit cells within the light modulating layer.
[0089] Several embodiments of the invention will now be described in more detail. Other embodiments of the invention can be envisioned by persons skilled in the art without departing from the technical teaching of the invention, the invention being limited only by the terms of the appended claims.
[0090] With reference to FIG. 1 to FIG. 3, an optical microscope article according to a first embodiment is now described. The optical article 100, of which FIG. 1 and FIG. 2 are cross- sectional views, comprises an optically transparent base substrate 110, a light modulating layer 120 integrated with the base substrate 110, and a longpass filter layer 130 in optical communication with the light modulating layer 120. The base substrate 110 may be an optical flat and may comprise an optical glass or transparent polymer material. The light modulating layer 120 and the longpass filter layer 130 are respectively disposed at a first position Z1 and a second position Z2 along a longitudinal axis Z of the optical article 100, which typically coincides with the optical axis of the optical article. The light modulating layer 120 comprises a plurality of micro- or nanostructured unit cells 121 , which are arranged into an array and separated from each other by optional light-blocking regions 125. Each unit cell 121 comprises a transmissive metasurface 124 that acts as a meta-lens with respect to wavelengths comprised by a modulation band. The metasurfaces 124 of the different unit cells 121 comprises a geometrical arrangement or designed pattern of micro- or nanostructures, e.g. tiny optical elements such as pillars, posts, fins, optical antennas, slits or holes of sub-wavelength dimensions. The micro- or nanostructured elements of the metasurface may be formed directly in an outer surface portion of the base substrate 110 or may be formed in an intermediate layer that has been previously deposited onto the base substrate. Known lithographic patterning techniques such as DUV lithography and etching techniques may be used to define the individual optical elements of each metasurface 124 in the light modulating layer 120, wherein the patterning follows a meta-lens design. For instance, silica-based pillar structures of sub-wavelength may be obtained in a silica-based base substrate by etching away the excess material between neighboring pillars, wherein the individual position and diameter of each pillar has been selected in accordance with the desired light convergence properties of the resulting metasurface. Optionally, a protective coating 126 may be applied to the metasurfaces 124. In the present embodiment, the light modulating layer 120, the base substrate 1 10 and the longpass filter layer 130 are stacked along the longitudinal device axis Z to form a single integrated stack of thickness T and width dimension W. The light modulating layer 120 and the longpass filter layer 130 may be integrally formed at or attached to opposite sides of the (common) base substrate 110, e.g. a glass or polymer substrate. A common material system, e.g. dielectrics, may be used for the manufacture of the light modulating layer 120 and the longpass filter layer 130. Typically, the optical article 100 is provided in a compact and ultrathin format such that W » T.
[0091] Furthermore, each unit cell 121 of optical article 100 has light convergence properties akin to a lens. The metasurface 124 within each unit cell 121 reshapes collimated or divergent light beams / bundles to converge them into small volume. Light bundles L1 , L2 and L3 originating from distinct points OP1 , OP2 and OP3 in an object plane OP, placed at a distance d1 from the lightreceiving face 122 of the light modulating layer, are transmitted through the light modulating and longpass filter layer 120, 130 and focused into respective spots P1 , P2 and P3 of an image plane IP placed at a corresponding distance d2 from a light-transmitting rear face 123 of the light modulating layer. The spots P1 , P2 and P3 in the image plane IP are images of the original object point OP1 , OP2 and OP3 in the object plane OP. In an optical microscope (not shown) comprising the optical article 100, a detector, e.g. a CMOS detector, may be positioned in the image plane IP to record transverse coordinates of the spots P1 , P2 and P3 in the detector / image plane together with their intensity / energy values. Imaged object points, e.g. the spots P1 , P2 and P3, are preferably obtained at distances d2 < 10 cm or less. The imaging distance d2 may have a lower limit that is governed by the effective focal length associated with the meta-lens of each unit cell. This lower limit may be met for incident light beams / bundles that originate at optical infinity relative to the lightreceiving face of the light modulating layer. The effective focal length of the meta-lenses may be about 100 pm to 1 mm. Although unit cells 121 as shown in the present embodiment have the same effective focal length, yielding the same imaging distance d2 for equal object point distance d1 , different unit cells may include metasurfaces with lens-like properties that have different associated effective focal lengths in other embodiments of the invention. Moreover, it is possible to include unit cells of a second kind in the light modulating layer that do not exhibit light convergence properties within the modulation band but have no functionality or a different type of optical functionality.
[0092] It may be convenient that all or selected unit cells have a broader FOV compared to their respective lateral sizes, whereby multi-copy images of the objects in the object plane OP are created in the image plane IP. This enables both enhanced depth resolution and photon efficiency of the optical device. FIG. 2 illustrates the formation of multi-copy images by the central unit cell that converges light bundles LT and L3’, respectively originating from points OP1 and OP3 in the object plane OP, towards the additional spots P1 ’ and P3’ in the image plane image IP, respectively. As shown, the light bundles LT, L2, and L3’ are situated within the FOV of the central unit cell, which extends beyond the lateral dimension of the central unit cell.
[0093] As indicated in the figure, the object point OP1 may correspond to the location of a fluorescent marker (fluorophore) on an object of interest O. Light cone L1 may be the fluorescent light that the marker emits in response to a wide beam of excitation light EL. In contrast to the emitted light in the bundles L1 and L2, the wavelength of the excitation light beam EL is inferior to a cut-on wavelength of the longpass filter layer 130 and is blocked by absorption and / or reflection, depending on the nature (absorbing or reflective) of the longpass filter in layer 130. Excitation light EL is filtered out by the longpass filter layer 130 and is thus absent in the half-volume extending outwardly from the rear face 127 of the optical article 100. The distinctive cut-on wavelengths for the modulation band MB - the operational wavelength range in which different metasurfaces 124 of the light modulating layer 120 exhibit lens-like properties- and the longpass filter layer 130 are shown at respective spectral locations A1 and A2 along the wavelength axis A in FIG. 3. As can be seen, the spectral transmittance curve LP of the longpass filter layer 130 (spectral filter response) has a pronounced, sharp edge LPE at the cut-on wavelength A2, which is superior to the cut-on wavelength A1 of the modulation band MB. The excitation light EL is confined in a spectral region that falls outside the spectral transmittance curve LP and its further propagation is therefore blocked by the longpass filter layer 130, e.g. the longpass filter layer 130 acts as an emission filter for the fluorescent light L1 , L2 at longer wavelengths compared to the cut-on wavelength A2.
[0094] FIG. 4 illustrates different arrayed arrangements of unit cells of the light modulating layer in accordance with embodiments of the invention. The light modulating layer of the optical device may extend in a two-dimensional surface, e.g. a plane P. The unit cells 121 may be understood as tiles that are arranged at various positions across the plane P to cover or fill a surface area A of the plane P. In one example, the unit cells 121 are arranged in a linearfashion along a principal direction (elongation axis) of the light modulating layer 120 and the corresponding optical device. This defines a linear one-dimensional array 410 of unit cells 121 , which can be useful in applications that require line imaging or line scanning. In another example, the unit cells 121 are arranged along two principal directions (e.g. X and Y axis, corresponding to a width and length direction of the device) of the light modulating layer 120 and the corresponding optical device. This defines a regular two-dimensional array 420 of unit cells 121 , e.g. a 7x3 array in this example. However, the unit cells do not have to be positioned in accordance with a rectangular grid. In another example, unit cells 121 are arranged along an angular and a radial direction of the light modulating layer 120. In embodiments of the invention, a transverse dimension L of each unit cell in a direction perpendicular to the longitudinal device axis Z may be about 1 cm or less. A gap, G, between adjacent unit cells may be about 1 mm or less, e.g. smaller than 100 pm, and a thickness of each unit cell in the direction of the longitudinal axis Z may be less than 100 pm. Unit cell arrays count at least two cells and more preferably comprise tens to hundreds of cells. A zoomed-in portion 430 of a unit cell is reveals a plurality of micro- or nanostructured elements 431 that project vertically from a supporting base 432 and act as scattering centers with respect to incident light beams, i.e. create a large number of scattered waves. For example, pillar structures of sub-wavelength dimensions (e.g., nanopillars) extend vertically from a planar base, e.g. an outer face of the base substrate 110. The pillar or rod elements 431 are preferably formed of a CMOS-compatible material such as silicon, titanium oxide, silicon nitride, silicon dioxide, gallium nitride, etc., which has a higher associated refractive index than the material or medium that extends between the individual elements 431 , e.g. air. The collection of micro- or nanostructured elements 431 are arranged in a geometrical pattern that causes a coherent interaction between the many scattered waves, which results in the positive increase irradiance and the convergence of light in an observation plane placed at a distance from the light-transmitting surface of the light modulating layer. The above-described arrayed arrangements are non- exhaustive and non-limiting. The skilled person may define other arrangements. Similarly, the boundaries of the unit cells are not a limiting feature. Unit cell boundaries may have shapes that are different from the shown circular and square-like shapes.
[0095] FIG. 5 is a cross-sectional view of an optical device according to a second embodiment. The optical device 500 differs from the previous embodiment in that the light modulating layer 120 and the longpass filter layer 130 are applied to the same side instead of opposite sides of the base substrate 110. In the present embodiment, the longpass filter layer may be deposited and formed first during manufacture, followed by the deposition and structuring of the light modulating layer. Nonetheless, the relative order in which the light modulating and longpass filter layer are formed on the same face of the base substrate may be reversed. That is, the respective positions of the light modulating layer and the longpass filter layer along the device axis Z may be interchanged such that Z2 > Z1 , instead of Z2 < Z1 as shown in the figure.
[0096] FIG. 6 is a cross-sectional view of an optical device according to a third embodiment. The optical device 600 differs from the previous embodiments in that the light modulating layer 120 and the longpass filter layer 130 are formed on different substrates 110, 610. More specifically, the light modulating layer 120 is integrated with the base substrate 110 as before, whereas the longpass filter layer 130 is formed on a second substrate 610 that is spaced at a distance from the base substrate 110 along the longitudinal device axis Z. This distance may be controlled accurately by the thickness of one or more spacing elements 611 that are arranged between a lower outer face of the base substrate 110 and an upper outer face of the longpass filter layer 130 on the second substrate 610. The spacers 611 may be arranged at a circumference of the longpass filter layer and may even protrude from the longpass filter layer in a plane perpendicular to the longitudinal device axis Z (not shown) to circumferentially enclose the connecting region between the base substrate 110 and the longpass filter layer 130. The space 612 between the base substrate 110 and the longpass filter layer 130 that is not occupied by the spacers 611 may comprise a transparent filling medium, e.g. a refractive index matching fluid, vacuum or air.
[0097] The spacers 611 may be adhesive or an adhesive substance may be applied to the spacers 611 to securely stack and firmly attach the second substrate with longpass filter layer 130 to the base substrate. Alternatively or additionally, an adhesive substance may be provided in the space 612.
[0098] In a variant of this embodiment, a lower outer face of the second substrate 610, opposite to the longpass filter layer 130, may be facing the lower outer face of the base substrate 110 instead of the longpass filter layer, e.g. the second substrate 610 with longpass filter layer 130 may be flipped vertically before attaching it to the base substrate 110. Likewise, it is possible to flip the base substrate 1 10 such that the light modulating layer 120 is facing either one of the longpass filter layer 130 and the lower outer face of the second substrate 610 opposite to the longpass filter layer 130.
[0099] FIG. 7 is a cross-sectional view of an optical device according to a fourth embodiment. The optical device 700 differs from the third embodiment in that the two distinct substrates 110, 610 are bonded together by means of an intermediate bonding layer 701.
[0100] FIG. 8 is a cross-sectional view of an optical device according to a fifth embodiment. The optical device 800 differs from the previous embodiments in that it includes an additional color filter layer 830. The color filer layer 830 is located at position Z3 along the longitudinal device axis Z and, in the plane perpendicular to the longitudinal axis Z, is subdivided into areal portions or tiles. Each tile of the color filter layer is associated with a respective one of the unit cells 121 or a respective group of neighboring unit cells of the light modulating layer 120 (e.g. one-to-one or many-to-one correspondence between unit cells of the light modulating layer and tiles of the color filter layer) . This means that center positions of the different tiles of the color filer layer 830 in the plane perpendicular to the longitudinal axis, e.g. the X-Y plane, are substantially aligned with the center coordinates of the corresponding unit cells in the light modulating layer 120 and an area projection of each tile of the color filter layer 830 onto this X-Y plane, e.g. when the device 800 is viewed along the Z-axis, overlaps and encompasses the area projection of the corresponding unit cell of the light modulating layer 120 onto the same X-Y-plane. Moreover, each tile of the color filter layer 830 is associated with a color filter unit characterized by a corresponding filter passband. Tiles at different positions within the color filter layer can have different non-overlapping or partially overlapping filter passbands, meaning that the color filter layer 830 provides position-dependent filtering of incident light. Color filter units at different positions inside the color filter layer 830 can therefore have different associated passband center wavelengths. For example, a first group of color filter units 830a is transmitting light within a first wavelength band (e.g. first color channel), a second group of color filter units 830b is transmitting light within a second wavelength band (e.g. second color channel) and a third group of color filter units 830c is transmitting light within a third wavelength band (e.g. third color channel). In embodiments of the invention, the color filter units of the different groups may be positioned alternatingly inside the color filter layer, thereby creating a color filter array in which color filter unit 830a of the first group are interleaved with color filter units 830b of the second group and color filter units 830c of the third group. The number of color filter groups is not limited to three distinct filter groups but there may be any reasonable number of filter groups present in the color filter layer, e.g. one filter group, two filter groups, three filter groups or more than three filter groups. In the case of a single filter group, the different tiles may be indistinguishable from each other, or tiling may be absent altogether, leaving just one uniform color filter layer having a single associated filter passband. In embodiments of the invention, the filter passbands associated with different groups of color filter units are typically comprised by the modulation band MB and preferably have little crosstalk. Furthermore, the different groups of color filter units may be configured to have at least one common transmission band (additional filter passband) outside the modulation band MB. This has the advantage that unmodulated light at wavelengths beyond the modulation band MB can pass through the light modulating layer and the color filter layer without much hindrance, which is beneficial to digital inline holographic microscopy methods using the optical device.
[0101] As indicated, the color filter layer 830 may be integrated with the base substrate 1 10, e.g. formed on a face of the base substrate that is opposite to the longpass filter layer 130. However, the color filter layer 830 may also be provided on the same side of the base substrate as the longpass filter layer or formed on a different substrate to be affixed to the base substrate, as explained with reference to the preceding embodiments. Furthermore, the light modulating layer 120, the longpass filter layer 130 and the color filter layer 830 may be positioned in any order along the longitudinal axis Z. Accordingly one may have any of the following orderings of layers: Z1 > Z2 > Z3, Z1 > Z3 > Z2, Z2 > Z1 > Z3, Z2 > Z3 > Z1 , Z3 > Z1 > Z2, Z3 > Z2 > Z1 .
[0102] The color filter layer 830 may be obtained by deposition of materials of varying or alternating refractive index, thus creating an interference color filter. Position-encoding masks may be used to create differences in the deposited material or the deposited material thicknesses, which results in the different groups of color filter units. The deposited materials of the color filter layer may be CMOS-compatible dielectrics such as low-conductivity silicon, silicon oxide, silicon nitride, titanium oxide, gallium nitride, etc. Alternatively, the color filter units of the color filter layer 830 may be obtained through dye-doping of the different sites of the color filter units (absorption-based color filters).
[0103] In fluorescent microscopy applications, the color filter layer 830 provides a means for obtaining color image information, e.g. obtain separate image regions of the same object for each color channel, at the cost of slightly reduced resolution. Objects of interest may be labeled with different fluorescent markers whose respective emission wavelengths can be separated by the different color channels of the color filter layer. Each unit cell of the light modulating layer focuses object points marked by the fluorophores into a different spot in the image plane. The different color filter units associated with the unit cells of the light modulating then filter the converging light beams such that only light within the desired color channels reaches the image plane. It is also possible to adapt unit cells of the light modulating layer to have different effective focal lengths such that converging light beams related to different color channels are focused at corresponding different distances from the light-transmitting rear face of the light modulating layer. This illustrates the fact that in embodiments of the invention unit cells of light modulating layer be designed independently from the longpass filter layer and that the metasurfaces of the different unit cells may have different convergence properties.
[0104] FIG. 9 is a cross-sectional view of an optical device according to a sixth embodiment. The optical device 900 differs from the previous embodiments in that the light modulating layer 120 comprises multiple sub-layers 120a-b. Respective metasurfaces 124, 924 are patterned into each sub-layer 120a, 120 b. That is, each sub-layer 120a, 120b comprises a pattern of micro- or nanostructures which confer light shaping properties to the sub-layer of the unit cell. In consequence, each unit cell 121 of the light modulating layer may include a stack of metasurfaces, e.g. a first metasurface 124 and a second metasurface 924 which are stacked along the longitudinal device axis Z. In embodiments of the invention, each metasurface may extend throughout the corresponding layer or sub-layer (i.e. metasurface thickness is equal to layer / sub-layer thickness) or only a portion thereof (i.e., metasurface thickness is equal to layer / sub-layer thickness). In a unit cell of the light modulating layer comprising more than just a single metasurface, adjacent metasurfaces of the stack may be separated by a gap of 1 ,0 pm to 1 ,0 mm. The first metasurface 124 exhibits the above-described light convergence properties, i.e. acts as a meta-lens withing the modulation band MB. The additional metasurface 924 may be configured to complement the operation of the first metasurface 124 as a meta-lens inside the modulation band, by enhancing or improving the light convergence properties. For instance, the additional metasurface may increase the efficiency with which the impinging light beams are focused into spots at a distance from the light-transmitting face 123 of the light modulating layer 120, correct aberrations associated with the meta-lens implemented by the first metasurface 124, extend the achromatic focusing of the first metasurface 124, etc.
[0105] Additionally or alternatively, the further metasurface 924 may fulfill other light shaping requirements of the optical device, e.g. select a specific polarization component of the incident light beams or modulate the spectral response of the first metasurface 124 to obtain multiple distinct spots in the image plane with respect to correspondingly distinct polarization states and / or wavelength bands within the modulation band MB. Alternatively, further metasurface 924 modulates the amplitude and phase properties of the light traversing it. This modulation can be a spatially uniform or spatially varying modulation, complementing the function of the first metasurface layer 124. Embodiments of the invention are not limited to groups of two stacked metasurfaces as shown in Fig. 6 but can comprise more than two layers with respective metasurfaces, each providing specific or supplementary functionality, thus obtaining a light modulating layer that implements multiple functionalities. The multiple metasurface comprising unit cells of the light modulating layer are compatible and can be combined with any of the preceding embodiments, including the possibility of having a color filter layer.
[0106] In other embodiments of the invention, more than two metasurfaces may be stacked in each unit cell of the light modulating layer. In yet other embodiments, a supplementary light modulating layer may be provided as part of the optical device, which may or may not be formed on the base substrate. For instance, the first light modulating layer and the supplementary light modulating layer may be provided on opposite sides of the base substrate. The supplementary light modulating layer may contain one or more metasurfaces which would otherwise be stacked within the first light modulating layer.
[0107] FIG. 10 is a cross-sectional view of an optical device according to a seventh embodiment. The optical device 1000 differs from the previous embodiments in that the light modulating layer 120 is provided with means for switching on and off the light convergence properties of the unit cells 121. An exemplary actuation mechanism may comprise a pair of electrodes 1001 and 1002, e.g. patterned and / or transparent electrodes, which are connectible to an external voltage source 1003. The electrode pair 1001 , 1002 is adapted to deliver a voltage signal to the metasurface of each unit cell 121 of the light modulating layer 120, which switches off the lens properties of the lens properties of the metasurfaces. The voltage signal may induce an electro-optical response of the metasurfaces, which reduces or eliminates any refractive index contrast between the micro- or nanostructured surface elements (e.g. pillars, holes, etc.) and the medium that extends between these surface elements. This can successfully suppress the scattering and / or diffracting of incident light beams by the plurality of the micro- or nanostructured surface elements in each unit cell in a controlled manner; the light modulating layer therefore stops having light convergence properties and simply transmits the impinging light. Removal of the voltage signal between the electrodes 1001 and 1002 restores the lens properties of the metasurfaces. In variants of this embodiment, heating electrodes or stretchable electrodes may be used to cause a similar suppression or weakening of the lens properties of the different metasurfaces through thermo-optic or photoelastic effects. In yet other variants, a refractive index matching fluid may be controllably supplied to and withdrawn from the open space between and surrounding the micro- or nanostructured surface elements in each unit cell of the light modulating layer, which similarly suppresses the scattering and / or diffracting of incident light beams by the plurality of the micro- or nanostructured surface elements. Means for switching on and off the light convergence properties of the unit cells of the light modulating layer are compatible and can be combined with any of the preceding embodiments, including the possibilities of having a color filter layer and / or multiple metasurfaces within the unit cells of the light modulating layer.
[0108] With reference to FIG. 11 to FIG. 14, the use of the optical device in a multi-modal optical microscope is now explained. The multi-modal optical microscope 1100 comprises an optical device 1110 in accordance with embodiments of the invention, an illumination unit 1140 and an image sensor 1130. It is advantageous to co-integrate the image sensor 1130 with the optical device 1 110 to achieve a very compact and alignment-free and scanning free image formation and detection module. For instance, the optical device 1 110 may be bonded directly onto a light-sensitive detector surface of the image sensor 1130. Nonetheless, it is possible to assemble the image sensor and the optical device as two non-integrated parts. A large single image sensor 1130 can be replaced by multiple smaller image sensor tiles in alternative embodiments. As explained before, the optical device 1110 includes the light modulating layer 120 formed on the base substrate 110, the longpass filter layer 130 and further includes a color filter layer 140. The color filter layer 140 may be a uniform color filter layer with a single filter passband associated with single-color imaging modalities or may be a non-uniform (e.g. tiled) color filter layer that includes different groups of color filter units and has multiple distinct filter passbands associated with multi-color imaging modalities. A holding member 1120 such as a bracket, sleeve, mounting tray, etc., may be configured to receive the optical device 1110 and the image sensor 1 130 in a predetermined location and orientation with respect to the distantly arranged illumination unit 1140. The holding member may comprise a back plate 1121 and a transparent front plate 1122. Samples for study or objects of interest, O, may be applied to and are supported by the front plate 1122 during microscopy. In this case, the object plane OP lies just next to the front plate 1122. The image sensor 1130 is placed in the detector plane / image plane IP at a distance from the light-transmitting rear face of the light modulating layer 120. In some embodiments of the invention, the optical microscope may comprise means for adjusting the distance between the image sensor 1130 and the light-transmitting rear face of the light modulating layer 120.
[0109] The illumination unit 1140 is configured to selectively emit light in different wavelength regions or intervals of the optical spectrum, including excitation light EL for fluorescent microscopy at wavelengths inferior to the cut-on wavelength of the longpass filter layer 130, light for brightfield microscopy, BL, at wavelengths superior to the cut-on wavelength of the longpass filter layer 130 and falling both within the modulation band MB of the light modulating layer 120 and at least one filter passband of the color filter layer 140. Additionally, the illumination unit 1140 may be configured to also selectively emit light for digital holographic microscopy, DHL, at one or more wavelengths superior to both the cut-on wavelength of the longpass filter layer 130 and a cut-off wavelength of the modulation band MB. For optical devices 11 10 including a color filter layer 140, a common transmission band of all or selected color filter units exists outside the modulation band MB which ensures that the DHL light effectively reaches the image sensor 1130. The illumination unit 1140 may comprise a broadband light source or light emitting device and one or more filters that are selectable depending on the desired imaging modality. Alternatively, the illumination 1140 may comprise means for switching between several light source or light emitting devices, which emit at the appropriate wavelengths for each imaging modality. Light guiding components, beam collimation and / or beam shaping optical components may also be present in the light path of the illumination 1140.
[0110] Moreover, the illumination light source may comprise multiple light emitters or light emitting devices that irradiate samples on the front plane 1122 from various angles, e.g. at a plurality of different illumination angles. Alternatively or additionally, the illumination unit 1 140 may be adapted for source scanning, e.g. the illumination source is mounted movably with respect to the front plane 1122 and the optical device 1110 to irradiate samples from a plurality of different source directions. In yet another embodiment, the illumination unit 1 140 may be configured to sequentially emit a series of structured light patterns to illuminate the object plane.
[0111] Furthermore, phase-retrieval methods may be applied to reduce image noise when operating the optical microscope in brightfield mode. To this end, the illumination unit may further be configured to supply brightfield light BL of different wavelengths (discrete wavelengths or different wavelength bands within the second emission range).
[0112] FIG. 11 illustrates the operation of the optical microscope 1100 in the fluorescence microscopy mode, in which the illumination unit 1140 is configured to supply excitation light EL at its output (first emission range). Preferably, the supplied excitation light EL is spatially incoherent. The illumination unit 1140 may include one or multiple LED sources to achieve a spatially incoherent illumination across the object plane. The spectral properties of the excitation light supplied by the illumination unit 1 140 may be choses adequately as a function of the modulation band and any optional color filter units. Objects of interest, O, contain fluorescent markers (fluorophores) are irradiated and excited by the emitted light EL and re-emit fluorescence light FL at longer wavelengths, e.g. in the visible region. For simplicity, the FL light cone of a single object point is shown in the figure, but many fluorophores may emit FL light at various positions across the illuminated part of the object plane OP. The excitation light EL that impinges on the longpass filter layer 130 has a wavelength shorter than the cut-on wavelength of the longpass filter layer, thus preventing the further transmission of excitation light EL through the optical device 110 towards the image sensor 1130. In contrast thereto, the fluorescence light FL has longer wavelengths superior to the cut-on wavelength of the longpass filter layer 130 and is therefore transmitted to the light modulating layer 120. As the fluorescence light FL also falls into the modulation band MB of the light modulating layer 120, the meta-lens functionality of each unit cell of the light modulating layer 120 focus the fluorescence light FL onto the sensor plane IP, where multiple spots are detected as multiple images of the same point in the object plane OP from which the FL light cone was initially emanating. The color filter layer 140 further improves the image contrast by removing residual excitation light and stray light but transmits the FL light.
[0113] Example image portions 1101 formed by the different unit cell are shown on the right-hand side and may be detected in separate regions of the image sensor 1130. The images points or focused spots appear blurred since the numerical aperture (NA) of each individual unit cell is limited. However, an improved resolution for the full image frame 1 102 - corresponding to the larger aperture synthesized by a collection of unit cells - can be reconstructed from the image portions 1101 (sub-regions of the detected image frame) using known reconstruction techniques.
[0114] In a variant of the fluorescence microscopy mode, the color filter layer 140 comprises different groups of color filter units and corresponding filter passbands. This can be useful when objects in a sample have been marked with fluorescent labels that re-emit fluorescent light indifferent wavelength regions. The color filter units of the different groups then assist with the separation of the different fluorescent light components in the image plane IP and enable the reconstruction of multi-color fluorescent microscopy images.
[0115] FIG. 12 illustrates the operation of the optical microscope 1100 in the brig htfield microscopy mode, in which the illumination unit 1140 is configured to supply brightfield microscopy light BL at its output (second emission range). The same or similar spatial and temporal coherence properties may be chosen for the supplied excitation light EL and the brightfield light BL. Upon irradiation of the objects of interest, O, with the source light BL, scattering of the source light BL occurs at the boundaries, irregularities and optical inhomogeneities of the objects O. For simplicity, the scattered BL light cone related to a single object point is shown in the figure, but scattering of BL light typically occurs at various positions across the illuminated part of the object plane OP. The scattered brightfield light BL has wavelengths longer than the cut-on wavelength of the longpass filter layer 130 and falls both into the modulation band MB of the light modulating layer 120 and into the filter passband of the color filter layer 140. Therefore, the scattered BL light is subjected to the light convergence properties of the unit cells within the light modulating layer 120 and is focused onto the sensor plane IP, where the image spots are detected. Although not shown for the sake of better visibility, the unscattered BL light also propagates towards the image sensor 1130. However, the unscattered component of the BL light is out-of-focus, thus resulting in a homogenous background illumination of the image sensor 1130, which can be subtracted in a digital image post-processing step. By adjusting the illumination angle of the brightfield light BL emitted by the illumination unit 1140, the impact of the unscattered forward component of the BL light can be reduced or even eliminated at the image sensor 1130.
[0116] FIG. 13 illustrates the operation of the optical microscope 1100 in the Fourier ptychography microscopy mode. The optical microscope 1100 is set up as described in FIG. 12, with the illumination unit 1140 configured to sequentially illuminate the sample objects with light in the second emission range (e.g. brightfield light BL) from a plurality of different angles. The illumination unit 1140 may be programmed to move along a scan path. Additionally or alternatively, the illumination unit 1 140 may be configured to irradiate the sample objects with structured illumination patterns in the second emission range. A series of images is captured by the image sensor 1130 while varying the illumination angle and / or structure patterns incident on the sample. Each illumination angle and / or pattern interacts with the sample's spatial frequencies differently, providing distinct information about the sample's structure. The meta-lenses of the unit cells in the light modulating layer 120 focus the light transmitted through the sample onto the image sensor 1130. The captured images are then computationally processed using Fourier ptychography algorithms. By combining the information from the multiple illumination angles and / or patterns, a high- resolution, wide-field image of the sample is reconstructed. The reconstructed image exhibits improved spatial resolution and depth of field compared to a single low-resolution image captured in the brightfield mode.
[0117] FIG. 14 illustrates the operation of the optical microscope 1100 in the digital (inline) holographic microscopy mode. In the holographic microscopy mode, the illumination unit 1140 is configured to irradiate the object O to be imaged with a collimated reference beam of source light selected from a third emission range, DHL, beyond the modulation band MB of the light modulating layer 120. For instance, light at about 700 nm wavelength or more may be used for the third emission range. The light scattered by the sample interferes with the reference beam, creating a hologram pattern on the image sensor 1130. The light modulating layer 120, longpass filter layer 130 and color filter layer 140 are designed to minimally disturb the reference beam and the light scattered by the object O. An image of the object O can be computationally reconstructed from the recorded holographic interference pattern, using known holographic reconstruction algorithms, to obtain the complex amplitude and phase information of the objects in the sample. The reconstructed holographic image provides quantitative information about the sample objects' three-dimensional structure. By selecting the wavelength of the reference beam outside the modulation band MB of the light modulating layer 120, the optical device 1110 enables holographic imaging without significant interference from the light modulation process. This demonstrates the capability of the device to perform holographic imaging in a compact and integrated manner.
[0118] Raw images recorded with an optical microscope in accordance with embodiments of the invention may be subjected to a post-processing step to further improve image quality. To this end, a software component (e.g. program, middleware, or library) may be provided for execution on a dedicated processing unit that is part of the image sensor hardware or a processing unit that is external to the image sensor hardware, e.g., a general-purpose processor of a PC. The software component may comprise machine-executable instructions that cause the processing unit to perform the post-processing step. Such instructions may represent algorithms for image quality enhancement that operate on the raw images as recorded by the image sensor. Different types of enhancements and corresponding algorithms may be applied.
[0119] By way pf example, an image calibration may be performed, prior to other enhancement algorithms, to account for and compensate any known irregularities or imperfections of the optical microscope, including irregularities or imperfections due to color filters, meta-lenses or image sensor. Calibration files may be provided and loaded, which contain the relevant calibration rules to be applied to the raw images. Such calibration files can be generated via calibration methods involving known standards. These calibration methods can be simple methods of linear algebraic methods or optimization problems that minimize measurement errors.
[0120] Furthermore, the software component may comprise physics-based algorithms that account for the optical unit impulse response of the optical microscope. The unit impulse response may not directly yield an output image for interpretation by an end-user. For example, application of the unit impulse response may cause the creation of replicas, magnifications, diffused translations etc., of the original raw image. Although physics-algorithms based on the unit impulse response may alter the information content of the raw images, they are also known to be capable of enhancing the image quality. For instance, optical distortions, aberrations, residual nonuniformities of the magnification, etc., may all be addressed by the physics-based algorithms. Adequate inverse computational or machine learning methods can be applied conjunction with the unit impulse response to transform the raw image data to user-interpretable data, e.g., a potentially modified representation of the raw image data that is more suitable for visualizing or assisting the user with the interpretation of the imaged objects within a sample. Exemplary physics-based algorithms or transformations include but are not limited to Fourier transforms, deconvolution or optical wave propagation algorithms.
[0121] While the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive. Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, the disclosure and the appended claims. In the claims, the word “comprising” does not exclude other elements or steps, and the indefinite article “a” or “an” does not exclude a plurality. Any reference signs in the claims should not be construed as limiting the scope.
Claims
28Claims1 . An optical device (100) for use in an optical microscope (1100), the optical device comprising:- an optically transparent base substrate (110),- a light modulating layer (120) integrated with the base substrate (1 10) and disposed at a first position along a longitudinal axis (Z) of the optical device, the light modulating layer (120) comprising an array of micro- or nanostructured unit cells (121), each unit cell (121) comprising a transmissive meta-lens (124) to image objects (O) located at a distance from a light-receiving front face (122) of the light modulating layer (120) at a corresponding distance from a light-transmitting rear face (123) of the light modulating layer,- a longpass filter layer (130) in optical communication with one of the front face (122) and the rear face (123) of the light modulating layer (120) and disposed at a second position along said longitudinal axis (Z), wherein an operational wavelength range associated with the imaging of objects (O) by the individual meta-lenses (124) of the light modulating layer (120), referred to as modulation band (MB), has a cut-on wavelength (A1) that is smaller than or equal to a cut-on wavelength (A2) associated with a filter edge of the longpass filter layer.
2. The optical device (100) according to claim 1 , wherein the base substrate (110) is an optical flat.
3. The optical device (100, 800) according to any one of the preceding claims, further comprising a color filter layer (830) disposed at a third position along the longitudinal axis (Z) of the optical device, the color filter (830) comprising at least one filter passband falling into the modulation band (MB) of the light modulating layer (120).
4. The optical device (100, 800) according to claim 3, wherein the color filter layer (830) comprises multiple different filter passbands at corresponding different positions within the color filter layer, whereby different unit cells (121) of the light modulating layer (120) are associated with different filter passbands of the color filter layer.
5. The optical device (100) according to any one of the preceding claims, wherein each unit cell (121) of the light modulating layer (120) is further configured to transmit incident light at one or more wavelengths outside the modulation band (MB) without focusing light emanating from points on objects (O) located at said distance from the light-receiving front face (122) of the light modulating layer (120) into spots at said corresponding distance from the lighttransmitting rear face (123) of the light modulating layer.
6. The optical device (1000) according to any one of the preceding claims, further comprising a means (1001 ; 1002) for switching on and off the imaging of objects (O) by the meta-lenses (124) of the light modulating layer (120).
7. The optical device (100) according to any one of the preceding claims, the optical device having a device thickness T along the longitudinal axis (Z) and a device width W along a transverse axis, perpendicular to the longitudinal axis, wherein T:W < 1 ,0.
8. The optical device (100; 500) according to any one of the claims 1 to 7, wherein the longpass filter layer (130) is applied directly to the light modulating layer (120), or wherein the longpassfilter layer (130) and the light modulating layer (120) are formed on opposite faces of the base substrate (110).
9. The optical device (600; 700) according to any one of the claims 1 to 7, wherein the longpass filter layer (130) is formed on a filter substrate (610) distinct from the base substrate (1 10), the filter substrate and the base substrate being stacked along a longitudinal axis (Z) of the optical device.
10. An optical microscope (1 100) selectively operable as a brightfield microscope and a fluorescent light microscope, the optical microscope comprising:- the optical device (1 110) according to any one of the preceding claims, and- an illumination unit (1140) arranged to irradiate objects (O) to be imaged with source light, an emission wavelength range for the source light being selectable between a first emission range (EL) associated with excitation light and a second emission range (BL) associated with brightfield light when operating the optical microscope (1100) as fluorescent light microscope and brightfield microscope, respectively, the first and second emission range being non-overlapping wavelength ranges, wherein the second emission range (BL) is comprised by the modulation band (MB) of the light modulating layer (120) of the optical device, and wherein the cut-on wavelength (A2) of the longpass filter layer (130) of the optical device is situated between the first emission range (EL) and the second emission range (BL), whereby the longpass filter (130) blocks source light in the first emission range but transmits source light in the second emission range.
11. The optical microscope (1 100) according to claim 10, further comprising an image sensor (1130) in optical communication with the rear face of the light modulating layer (120) of the optical device, wherein the image sensor (1130) is preferably integrated with the optical device (1110).
12. The optical microscope (1 100) according to any one of the claims 10 to 11 , wherein the illumination unit (1140) comprises multiple light emitters configured to deliver source light in the second emission range (BL), and / or wherein the illumination unit (1140) is configured to irradiate the objects (O) to be imaged from various illumination angles.
13. The optical microscope (1100) according to any one of claims 10 to 12, wherein the illumination unit (1140) is arranged to irradiate the objects (O) to be imaged with a beam of source light selected from a third emission range (DHL) beyond the modulation band (MB) of the light modulating layer (120) of the optical device, thus operating as a holographic microscope.
14. The optical microscope according to any one of claims 10 to 13, further comprising a processing unit configured to correct digital representations of the objects (O) to be imaged from imaging artifacts of the optical microscope.
15. Use of the optical device (1110) according to any one of the claims 1 to 9 in a multi-modal optical microscope (1100), including at least a fluorescence microscopy mode and a brightfield microscopy mode, wherein excitation light (EL) used to illuminate objects of interest (O) in the fluorescence microscopy mode has shorter wavelengths than the cut-on wavelength (A2) ofthe longpass filter layer (130) of the optical device (1110) and brightfield light (BL) used to illuminate objects of interest (O) in the brightfield microscopy mode has wavelengths longer than the cut-on wavelength (A2) of the longpass filter layer (130) and falling into the modulation band (MB) of the light modulating layer (120) of the optical device.
16. Use of the optical device (1 110) according to claim 14, further including a digital holographic microscopy mode, wherein reference light (DHL) used to illuminate objects of interest (O) in the digital holographic microscopy mode has wavelengths beyond the modulation band (MB) of the light modulating layer (120) of the optical device.
17. An optical microscope (1 100) selectively operable as a brightfield microscope and a fluorescent light microscope, the optical microscope comprising:- a device holder for removably receiving and securing the optical device (1110) according to any one of the claims 1 to 9,- an image sensor (1 130),- an illumination unit (1140) arranged to irradiate objects (O) to be imaged with source light, an emission wavelength range for the source light being selectable between a first emission range (EL) associated with excitation light and a second emission range (BL) associated with brightfield light when operating the optical microscope (1100) as fluorescent light microscope and brightfield microscope, respectively, the first and second emission range being non-overlapping wavelength ranges, wherein the second emission range (BL) is comprised by the modulation band (MB) of the light modulating layer (120) of the optical device, and wherein the cut-on wavelength (A2) of the longpass filter layer (130) of the optical device is situated between the first emission range (EL) and the second emission range (BL), whereby the longpass filter (130) blocks source light in the first emission range from reaching the image sensor (1130) but transmits source light in the second emission range, wherein the device holder is configured to secure the optical device (1110) in a position in which the image sensor (1130) is in optical communication with the rear face of the light modulating layer (120) of the optical device.
Citation Information
Patent Citations
High-integration multi-mode microscopic imaging device and method
CN115615968A
Microscopic observation apparatus, fluorescence detector, and microscopic observation method
US20210156803A1