An imaging device and a method for imaging

Abstract

An imaging device (100) for imaging of a sample (10) comprises: a light source (102) for illuminating the sample; a light modulator (110; 210; 310; 410) for receiving scattered light from the sample (10) and modulating the scattered light for altering an angular relation between angular propagation direction and spatial frequency information of the sample; and an image sensor (130) for detecting a plurality of sample representations based on sample information carrying light from the light modulator being incident on the image sensor; wherein the imaging device (100) is tunable between a first and a second mode for tuning an impact of the light modulator (110; 210; 310; 410) on the scattered light, wherein the light modulator (110; 210; 310; 410) outputs sample information carrying light with different angular relations in the first and second modes; and wherein the plurality of sample representations comprise sample representations detected in respective modes.

Description

[0001] AN IMAGING DEVICE AND A METHOD FOR IMAGING

[0002] Technical field

[0003] The present description relates to an imaging device and a method for imaging. In particular, the present description relates to imaging which need not involve a lens for forming an image of a sample.

[0004] Background

[0005] Holography is a method of producing three-dimensional images of an object or sample. Digital holography uses digital image sensors, such as a charge- coupled device (CCD) or a complementary metal-oxide-semiconductor (CMOS) image sensor.

[0006] Digital holography may be interesting to use in imaging of microscopic objects, because digital holography may be compact and scalable compared to conventional microscopy using lens-based images. However, spatial resolution based on imaging through digital holography may be inferior to conventional microscopy.

[0007] Therefore, it would be desired to provide an improvement to spatial resolution of imaging by digital holography.

[0008] Summary

[0009] An objective of the present description is to provide high resolution imaging through digital holography. A further objective of the present description is to also provide high quality imaging.

[0010] This and other objectives are at least partly met by the invention as defined in the independent claims. Preferred embodiments are set out in the dependent claims.

[0011] According to a first aspect, there is provided an imaging device for imaging of a sample, said imaging device comprising: a light source configured to illuminate the sample for forming scattered light being elastically or inelastically scattered by the sample; a light modulator configured to receive the scattered light from the sample and configured to modulate the scattered light for altering an angular relation between angular propagation direction within the scattered light and spatial frequency information of the sample carried by the scattered light, wherein the light modulator is configured to output sample information carrying light; and an image sensor comprising a plurality of light-sensitive elements, wherein each light-sensitive element is configured to generate a signal representative of intensity of light incident onto the light-sensitive element, wherein the image sensor is configured to detect a plurality of sample representations based on the sample information carrying light being incident on the plurality of lightsensitive elements; wherein the imaging device is configured to be tuned between at least a first mode and a second mode for tuning an impact of the light modulator on the received scattered light, wherein the light modulator is configured to present features defining a variable light modulating property in a cross-section of the light modulator perpendicular to a main propagation direction of the scattered light, wherein the imaging device is configured to control impact of the light modulating property on the received scattered light using a single signal for controlling impact of the light modulating property of a plurality of features, wherein the imaging device is configured to apply a first setting in the first mode and a second setting in the second mode, the second setting being different from the first setting, wherein the light modulator is configured to output sample information carrying light with different angular relations in the first and second modes; and wherein the plurality of sample representations comprise a first sample representation detected for the first mode of the imaging device and a second sample representation detected for the second mode of the imaging device.

[0012] Thanks to the imaging device comprising a tunable light modulator, the imaging device may be used in a versatile manner for forming sample representations using different settings. This may allow the imaging device to be used in different ways for imaging of samples with different settings. Further, the imaging device may be used for providing a plurality of sample representations of the same sample using different settings so as to acquire more information of the sample.

[0013] According to an embodiment, the light modulator is configured in the first mode of the imaging device to provide a unitary response to scattered light, wherein the image sensor is configured to detect a holographic image in the first sample representation, and wherein the light modulator is configured in the second mode of the imaging device to provide a shaping of a point spread function, wherein the image sensor is configured to detect a fluorescence image in the second sample representation.

[0014] Thus, the imaging device may be altered so as to be used for providing a holographic image or fluorescent imaging of a sample. The holographic image may be provided by detection of an interference pattern between light scattered by the sample, and non-scattered light. The fluorescence image may be provided by detection of light spread by the sample through fluorescence. Thus, the fluorescence image may be detected by detecting a point spread function, which may be obtained by the sample being imaged without use of an imaging lens. The detection of the fluorescence image may be referred to as fluorescence lens-free imaging.

[0015] In particular, the imaging device may be configured to provide a holographic image through in-line digital holography (wherein the nonscattered light travels along a common path with light that interacts with the sample). The in-line digital holography is based on detection of an interference pattern between scattered light and non-scattered light. In order for the interference pattern to be properly detected, it may be desired that light travels through a uniform medium between the sample and the image sensor. On the other hand, the fluorescence image may be advantageously provided by using a non-uniform layer between the sample and the image sensor for producing specific point spread functions. The fluorescence signal measured by the image sensor may then be deconvolved using information of the point spread functions to allow accurate detection of the sample by measuring the fluorescence signal.

[0016] According to an embodiment, the light modulator is configured in the first mode of the imaging device to provide a unitary response to scattered light, wherein the image sensor is configured to detect a holographic image in the first sample representation, and wherein the light modulator is configured in the second mode of the imaging device to provide a shaping of a point spread function, wherein the image sensor is configured to detect a fluorescence image in the second sample representation.

[0017] As used herein, a non-uniform optical layer implies a layer having a features on a surface of the layer such that the surface is not smooth. The features may thus affect refraction of light. The features are provided over an area of the surface.

[0018] The light modulator may be configured to be tuned between the first mode and the second mode such that light scattered by the sample selectively passes a non-uniform interface or a uniform interface.

[0019] According to an embodiment, the light modulator comprises a non- uniform layer configured to provide the shaping of the point spread function, wherein the light modulator is further controllable in the first mode for arranging a refractive index matching medium in contact with the non-uniform layer for forming a uniform interface.

[0020] For instance, the light modulator may comprise a second layer arranged in parallel with the non-uniform optical layer forming a gap between the second layer and the non-uniform optical layer. The gap may be selectively filled by a refractive index matching medium having a same refractive index as the non-uniform optical layer, or by another medium. This implies that the non-unitary response on light provided by the features of the non-uniform optical layer may be smoothened or unified such that the light scattered by the sample passes a uniform interface. In the second mode, the gap may be filled by air or another medium having a refractive index differing from the refractive index of the non-uniform optical layer.

[0021] The light modulator may be tuned between the first mode and the second mode by controlling the medium being arranged in the gap between the second layer and the non-uniform optical layer.

[0022] According to another embodiment of the first aspect, there is provided an imaging device for imaging of a sample, said imaging device comprising: a light source configured to illuminate the sample for forming scattered light being elastically or inelastically scattered by the sample; a light modulator configured to receive the scattered light from the sample and configured to modulate the scattered light for altering an angular relation between angular propagation direction within the scattered light and spatial frequency information of the sample carried by the scattered light, wherein the light modulator is configured to output sample information carrying light; and an image sensor comprising a plurality of light-sensitive elements, wherein each light-sensitive element is configured to generate a signal representative of intensity of light incident onto the light-sensitive element, wherein the image sensor is configured to detect a plurality of sample representations based on the sample information carrying light being incident on the plurality of lightsensitive elements; wherein the imaging device is configured to be tuned between at least a first mode and a second mode for tuning an impact of the light modulator on the received scattered light, wherein the light modulator is configured to present features defining a variable light modulating property in a cross-section of the light modulator perpendicular to a main propagation direction of the scattered light, wherein the imaging device is configured to control impact of the light modulating property on the received scattered light using a single signal for controlling impact of the light modulating property of a plurality of features, wherein the imaging device is configured to apply a first setting in the first mode and a second setting in the second mode, the second setting being different from the first setting, wherein the light modulator is configured to output sample information carrying light with different angular relations in the first and second modes; and wherein the plurality of sample representations comprise a first sample representation detected for the first mode of the imaging device and a second sample representation detected for the second mode of the imaging device.

[0023] When light is scattered by a sample, a diffracted light wave may be formed by light interaction with the sample. The diffracted light wave may comprise spatial frequency components, wherein small features of the sample affect high spatial frequency components of the diffracted light wave. Thus, in order to allow high resolution imaging, information carried by high spatial frequency components of the diffracted light wave should be detected and analyzed. The smaller size of features that is to be imaged (i.e., the higher resolution of imaging), the higher spatial frequency components need to be detected.

[0024] Further, high spatial frequency components of the diffracted light wave may be spread into large angles in relation to a main direction of light. Thus, illumination light that illuminates the sample may define a main propagation axis. The scattering of light by the sample may cause light to be scattered into a forward direction with a main propagation axis of the scattered light being a continuation of the main propagation axis of illumination light.

[0025] The image sensor may be configured to receive light incident on the light-sensitive elements, wherein the light sensitive elements are sensitive to light incident within an acceptance angle in relation to light incident along a normal to a plane in which the light sensitive elements are arranged. The image sensor may be arranged such that the main propagation axis of the scattered light may coincide with the normal to the plane in which the light sensitive elements are arranged. This implies that light scattered into large angles from the main propagation axis may not be within the acceptance angle of the light-sensitive elements of the image sensor.

[0026] Thanks to the use of the light modulator, propagation direction of scattered light may be changed. This implies that the light modulator may affect scattered light such that light scattered into large angles from the main propagation axis may be diverted into making a smaller angle to the main propagation direction. This may be used such that high frequency components of scattered light may be affected so as to be incident on the light-sensitive elements within the acceptance angle and be detected by the image sensor.

[0027] Hence, thanks to the imaging device comprising a light modulator, the imaging device enables scattered light to be controlled such that high frequency components may be detected. In other words, the imaging device facilitates detection of high spatial frequency components of scattered light scattered by the sample. This implies that high resolution imaging may be provided based on detection of the scattered light being modulated by the light modulator.

[0028] Thanks to the imaging device being tunable for tuning impact of the light modulator, sample representations may be detected by the imaging device using different settings. The plurality of sample representations thus provide diversity in settings under which the sample representations are detected. This diversity may be used in processing of the sample representations providing high quality imaging of the sample. For instance, artifacts may be caused by missing phase information in detection of the light that has been scattered by the sample. Such artifacts may be removed based on the plurality of sample representations being detected with different settings.

[0029] The possibility of setting the imaging device in at least two modes implies that the imaging device may be used for providing versatile imaging of the sample. Thus, the first and second modes may be used in different manners depending on application. As mentioned above, the first and second modes may be used for providing diversity, such as phase diversity, in imaging allowing sample representations to be combined for improving image quality. However, the first and second modes may be used in other manners. For instance, a sample representation acquired in the first mode may be used for controlling settings for acquiring the sample representation in the second mode. Thus, coarse imaging may be provided in the first mode, e.g., to identify regions of the sample to be further analyzed, and higher resolution imaging may then be applied in the second mode to such regions.

[0030] The light modulator may be controlled such that a repeatable transfer function may be provided for controlling the light modulating property of the light modulator. A control signal applied to the light modulator may provide a predictable output such that the light modulating property of the light modulator in response to the control signal may be determined and predicted. Thanks to a single signal controlling a plurality of features of the light modulator, the light modulator may be easily and quickly controlled for tuning of the light modulator. For instance, a single signal may be used for controlling the entire light modulator. However, it should be realized that more than one signal may be used for controlling the light modulator.

[0031] The imaging device need not comprise any lens for forming an image onto the image sensor. The image sensor may be configured to detect a light pattern formed in a plane defined by the plurality of light-sensitive elements. The light pattern may form a sample representation for imaging of a sample to be imaged. The plurality of sample representations may be further used for forming a reconstruction of the sample being imaged such that a visualization of the sample may be formed.

[0032] It should be realized that the imaging device need not necessarily be configured to form a visual representation of the sample that may be understood by a human observer. Rather, the sample representations may in themselves represent the sample without necessarily being further processed. The sample representations may for instance be used for analyzing the sample by processing the sample representations directly in a processing unit, without any reconstruction of the sample for forming a visualization of the sample being performed.

[0033] Thanks to the imaging device not necessarily having any lens, the imaging device may be very compact. In addition, the imaging device may facilitate imaging of a large field of view of the sample.

[0034] The imaging device may be configured to image any suitable sample. The sample may for instance be relatively transparent, such as a sample comprising cells or particles within a transparent liquid solution. This implies that an interference pattern may be detected by the image sensor, wherein the interference pattern is formed based on interference at the image sensor between scattered light and reference light formed by non-scattered light (i.e., light passing through the relatively transparent sample). However, it should be realized that back-scattered light may be detected instead of forward- scattered light. In such case, reference light for forming an interference pattern may be formed by specular reflection of light and the sample need not necessarily be transparent. Also, it should be realized that light from the light source may be divided into illumination light for illuminating the sample and reference light, such that the sample information carrying light may be combined with the reference light for forming the interference pattern to be detected. Thus, the reference light may take a completely different path than the light that interacts with the sample. This implies that samples can be imaged even if having low transmittance of light through the sample.

[0035] It should further be realized that the image sensor need not necessarily be configured to detect an interference pattern. Rather, the image sensor may be configured to detect only light that has been scattered by the sample. This may be used for providing a sample representation based on point spread function(s) for scattering of light.

[0036] It should be realized that the imaging device is not limited in relation to what can be imaged by the imaging device. However, the imaging device may advantageously be used for imaging of biological samples, such as any liquid sample in which one or more particles are arranged, or for imaging of biological objects, which may not necessarily be immersed in a liquid. Nevertheless, it should be realized that when referring to samples to be imaged, no limitation as to the imaging capability of the imaging device should be implied.

[0037] The light source may be implemented in many different manners. The light source may comprise one or more sources at which light is generated so as to form an origin of light. The light source may further comprise components for guiding light from the origin to a location at which emitted light is to be output.

[0038] The light source comprises at least one light-emitting element which is configured to output light towards the sample. The light-emitting element(s) may comprise source(s) for generating light, such that light may be generated in the light-emitting element(s). However, the light-emitting element(s) may alternatively form an output, such that light is generated in another location and guided to the light-emitting element(s) for being output by the lightemitting element(s). The source(s) for generating light may for instance be formed by a laser and / or a light-emitting diode (LED).

[0039] There are many different manners in which light may be scattered by a sample. The imaging device is not limited to any particular manner of scattering of light by the sample. Thus, the scattered light may be based on elastic or inelastic scattering of light by the sample, such as Tyndall scattering, Rayleigh scattering, or Mie scattering which does not change wavelength of light or Raman scattering or fluorescence which changes wavelength of light. The light modulator may be a spatial light modulator which is configured to form a spatially varying modulation of light. Thus, modulation of light may vary along a wavefront of light being incident onto the light modulator or along a cross-section of a beam of light. The light modulator may be configured to modulate at least one of phase, amplitude, or polarization of light.

[0040] The scattered light carries information of the sample in that scattering of light is dependent on, for instance, size, shape, and refractive index of features in the sample. The scattered light may carry spatial frequency information that represents spatial variation of properties in the sample. The spatial frequency information may be carried by the scattered light such that different frequencies propagate in different directions. Thus, there is a relationship between angular propagation direction of scattered light and spatial frequency information. The light modulator is configured to modulate the scattered light such that the angular relation may be changed. This affects how spatial frequency information may be detected by the image sensor and which frequencies are detected.

[0041] The light modulator comprises features that cause light modulation. These features may be defined by scattering or diffractive elements, such as particles, surface irregularities, lattice elements or refractive index variations. The features may be distributed within the light modulator for causing light modulation. The light modulator may be configured to control the impact of light modulation by the features based on a single signal controlling impact of a plurality of features. This may for instance be achieved by the single signal being configured to control a distribution of scattering or diffractive elements in the light modulator.

[0042] The light modulating property of the features may for instance cause modulation of phase, amplitude and / or polarization of light.

[0043] The imaging device can be tuned between the first mode and the second mode. The impact of the light modulator on the scattered light received by the light modulator is different for the different modes. The imaging device can be tuned between the first mode and the second mode by tuning the light modulator. Thus, the signal for controlling impact of the light modulating property may be a signal that affects the light modulator.

[0044] However, it should be realized that the imaging device may alternatively be tuned by tuning light that illuminates the sample. For instance, wavelength or polarization of light output by the light source may be tuned or the light source may be moved or rotated so as to tune a position in space from which light is output towards the sample or tune a direction of propagation of light towards the sample. This may imply that the impact of the light modulator is also changed, because the impact may be dependent on properties of the light, such as wavelength or polarization of the light. Thus, the signal for controlling impact of the light modulating property may be a signal that affects the light source or affects light output by the light source. Since the plurality of features of the light modulator may all be dependent on properties of the light, tuning of the light also controls impact of the plurality of features on the scattered light received by the light modulator.

[0045] The light source may also be tuned by selecting which light source(s) of a plurality of light sources that is to illuminate the sample. For instance, different light sources may provide different wavelength or polarization or may be mounted to output light at different positions in space or at different directions of propagation of light towards the sample. Thus, light that illuminates the sample may be simply tuned by selecting which light source(s) are allowed to output light for illuminating the sample.

[0046] The imaging device may be controlled between the first mode and the second mode by providing different signals for the different modes. This may imply that a signal is turned on for controlling the imaging device to the first mode and that the signal is turned off for controlling the imaging device to the second mode. However, the signal may alternatively have different characteristics for controlling the imaging device to the first mode and the second mode, respectively.

[0047] The image sensor may be any sensor being able to detect and form a representation of incident light. The light-sensitive elements of the image sensor may be arranged in a regularly ordered array. The light-sensitive elements may define a plane in which incident light is detected. The image sensor may for instance be formed by a complementary metal-oxide- semiconductor (CMOS) sensor or a charge-coupled device (CCD) sensor.

[0048] As used herein, the term “light” should be interpreted broadly, so as to include but not be restricted to visible light. Rather, the term light may imply other parts of the electro-magnetic spectrum, such as ultraviolet light or infrared light.

[0049] It should further be realized that the imaging device may provide a common housing in which the light source, the light modulator and the image sensor are arranged. The light source, the light modulator and the image sensor may be mounted in the housing so as to control their placement in relation to each other so as to provide desired propagation of light from the light source to illuminate the sample and of scattered light via the light modulator to the image sensor.

[0050] The imaging device may be configured to define a sample position in which a sample is to be placed for imaging. Thus, the imaging device may for instance comprise a carrier that may carry the sample into the sample position within the housing.

[0051] The light modulator may be planar defining a planar entrance surface and an opposite planar exit surface parallel with the entrance surface, wherein the light modulator is configured to receive the scattered light through the entrance surface and output sample information carrying light through the exit surface. The light modulator may be arranged such that a main propagation axis of the scattered light (i.e., a central axis such that light propagation is substantially symmetrical around the axis) is incident on the entrance surface along a normal of the entrance surface.

[0052] The image sensor may also be planar and may be arranged in parallel to the planar light modulator. Thus, a main propagation axis of light received by the image sensor may be incident along a normal of the image sensor.

[0053] However, it should be realized that the light modulator and / or the image sensor may be angled in relation to light propagation. An angle of the planar surface of the image sensor in relation to a main propagation axis of light affects angular direction of light that is within the acceptance angle of the light-sensitive elements.

[0054] According to an embodiment, the features defining the variable light modulating property have a size smaller than 10 pm, such as smaller than a wavelength of the scattered light.

[0055] The light modulator may be used for transferring light propagating at large angles in relation to the main propagation axis towards smaller angles. Having small size of features within the light modulator may ensure an efficient transfer of light in the changing of the propagation direction. The size of features may for instance be defined by a radius of a feature in the light modulator or a width or length of a feature.

[0056] According to an embodiment, the light modulator is configured to, at least in the second mode, apply modulation of the scattered light such that spatial frequency information of the scattered light is altered such that at least high spatial frequency content is directed from a first angle to a second angle in relation to a main propagation direction of the scattered light, wherein the second angle is smaller than the first angle.

[0057] It should be realized that spatial frequency information of scattered light may be distributed over a range of angular propagation directions. The distribution may be different for different spatial frequencies. Thus, a specific spatial frequency is not purely propagated in a single angular direction. Further, the modulation of scattered light may not completely alter propagation direction of all light propagating in a particular direction. Rather, the modulation of scattered light may affect the distribution of spatial frequency information of scattered light over the different angular propagation directions.

[0058] However, the light modulator may be configured to apply a modulation such that detection of high spatial frequency content of scattered light is improved. Thus, the light modulator may apply a modulation that causes a larger fraction of high spatial frequencies to propagate within an acceptance angle of the light-sensitive elements of the image sensor.

[0059] Spatial frequency may be measured by cycles or line pairs per millimeter. An inverse of the spatial frequency corresponds to a spacing between a line pair, indicating a feature size being resolved at the spatial frequency.

[0060] The imaging device may be configured to enable detecting high spatial frequency components, such as spatial frequency components corresponding to a resolution smaller than a size of a light-sensitive element of the image sensor. Thus, high spatial frequency content may correspond to spatial frequency components corresponding to a resolution smaller than a size of a light-sensitive element of the image sensor.

[0061] For instance, the imaging device may be configured to enable detection of spatial frequency components larger than 500 line pairs / mm. Thus, high spatial frequency content may for instance correspond to spatial frequency components larger than 500 line pairs / mm.

[0062] According to an embodiment, the imaging device is configured to be tuned between more than two modes and configured to apply different settings in different modes, wherein the imaging device is configured to reconstruct a visual image of the sample based on the plurality of sample representations detected for the more than two modes of the imaging device.

[0063] Thus, the imaging device may use a plurality of sample representations for providing reconstruction of a visual image of the sample. The plurality of sample representations may provide information diversity in representing the sample such that use of the plurality of sample representations enables reconstruction of a visual image of high quality and high resolution.

[0064] The imaging device may be configured to use ptychography for reconstructing a visual image based on the plurality of sample representations.

[0065] According to an embodiment, the light modulator is configured in the first mode of the imaging device to provide a unitary response to scattered light such that the light modulator in the first mode of the imaging device does not alter the angular relation.

[0066] Thus, the light modulator may in the first mode appear transparent to the scattered light received by the light modulator. This implies that no effect on the scattered light is provided by the light modulator.

[0067] Hence, even though light passes the light modulator before being detected, the light modulator need not necessarily affect the scattered light in the first mode. Thus, the imaging device may be utilized to acquire information or perform imaging of the sample as if no light modulator was present.

[0068] According to an embodiment, the imaging device is configured to perform coarse reconstruction of the sample based on the first sample representation.

[0069] Thus, the coarse reconstruction may be performed based on the first sample representation being acquired with the light modulator being set to provide the unitary response. This implies that coarse reconstruction may be performed without the light modulator affecting the scattered light, such that the light modulator need not be taken into account when determining the coarse reconstruction of the sample. Hence, processing for determining the coarse reconstruction may be relatively simple.

[0070] It should also be realized that coarse reconstruction may be determined based on more than one sample representation. For instance, the coarse reconstruction may be based on at least three sample representations that are acquired with different settings to provide information diversity so as to enable a higher quality reconstruction compared to using a single sample representation. The more than one sample representation used for coarse reconstruction may all be acquired using a unitary response for the light modulator. Thus, no tuning of the light modulator needs to be performed. Instead, a wavelength, polarization and / or spatial position of the light source may be tuned. Using the same setting for the light modulator may be useful for quickly acquiring the more than one sample representations, as the light modulator may not be very quickly tuned between different settings.

[0071] According to an embodiment, the imaging device is configured to use the coarse reconstruction of the sample for controlling a number of sample representations of different light modulator settings to be detected for high resolution reconstruction of the sample.

[0072] Hence, the coarse reconstruction may be used for controlling further acquisition of the sample representations. Thus, the imaging device may be controlled so as to efficiently acquire the necessary information (and not more) for detecting information of the sample to allow providing of a desired resolution of the imaging of the sample.

[0073] According to an embodiment, the imaging device is configured to use the coarse reconstruction of the sample for controlling a modulation pattern provided by the light modulator.

[0074] The light modulator may provide a modulation pattern that defines variation of the light propagation property of the light modulator. The modulation pattern may define the variation in a plane perpendicular to the main propagation direction of scattered light in the light modulator. The modulation pattern may be controlled by a single signal for controlling impact of the light modulating property on the light.

[0075] The modulation pattern may be controlled such that the modulation provided by the light modulator on scattered light may be controlled. The coarse reconstruction may be used for controlling the modulation pattern to suit the sample that is imaged by the imaging device. For instance, the modulation pattern may be controlled to achieve high signal-to-noise ratio of acquiring sample representations or for achieving high resolution of imaging of the sample.

[0076] According to an embodiment, the imaging device is configured to use the coarse reconstruction of the sample for controlling settings of the image sensor for detecting the sample representations.

[0077] Thus, the coarse reconstruction may further be used for controlling settings of the image sensor such that the settings are adapted to the sample. For instance, the imaging device may be configured to set a region of interest of the sample to be imaged at a higher resolution. Thus, the coarse reconstruction may be used to identify regions in which interesting features of the sample are present. Then, the imaging device may be controlled to only perform high resolution imaging for the region(s) of interest. This may ensure that processing speed in order to reconstruct an image may be improved as only the region(s) of interest may need to be reconstructed.

[0078] According to an embodiment, the light modulator is configured to, in at least one of the first and the second mode, apply a modulation pattern that is adapted to a type of sample to be imaged.

[0079] Requirements on acquisition of sample representations may depend on the type of sample. For instance, sparsity of features of the sample may differ between different types of samples. The modulation pattern may be adapted to provide suitable signal-to-noise ratio and / or image resolution. Thanks to using a modulation pattern that is adapted to a type of sample, the modulation pattern to be used may easily be determined. For instance, the type of sample may be determined based on a coarse reconstruction. Thereafter, the modulation pattern may be selected based on the type of pattern. Hence, the modulation patterns may be predetermined and need not be generated when imaging is to be performed.

[0080] According to an embodiment, the imaging device is configured to store settings of the light modulator for a plurality of different types of samples.

[0081] This implies that the modulation pattern may be quickly determined by being prestored in the imaging device. The imaging device may simply fetch the settings from a memory when needed.

[0082] According to an embodiment, the light modulator is configured to be tuned between the first and the second mode of the imaging device, wherein different settings of the light modulator in the first mode and the second mode provide different angular relations of the sample information carrying light between the first mode and the second mode.

[0083] Thus, the imaging device may be configured to provide tuning of the light modulator for tuning the impact of the light modulator on the received scattered light. The light modulator may thus be actively controlled. A tunable light modulator may provide a large degree of freedom in controlling the impact of the light modulator on the received scattered light.

[0084] According to an embodiment, the light source is configured to be tuned between the first mode and the second mode of the imaging device such that a characteristic of the illumination light is changed between the first mode and the second mode, wherein the light modulator is configured to alter the angular relation in dependence of the characteristic of illumination light to provide a different angular relation of the sample information carrying light between the first mode and the second mode.

[0085] A tunable light source may be used as an alternative to a tunable light modulator or may be used in combination with a tunable light modulator. This may provide further degrees of freedom in controlling the impact of the light modulator on the received scattered light.

[0086] By having a tunable light source, the light modulator need not be tunable. Thus, the light modulator may be a passive component which provides a fixed setting of the light modulating property, which may have a spatial variation in a cross-section of the light modulator. This implies that the light modulator may not be very complex as it may not need to be dynamically changed between different settings of the light modulating property.

[0087] According to an embodiment, the image sensor is configured to detect each of the plurality of sample representations as an interference pattern formed at a plane of the image sensor by the sample information carrying light output from the light modulator and non-scattered light from the light source.

[0088] Thus, the imaging device may be used for holographic imaging of the sample, wherein the interference patterns may be used for reconstructing a visual image of the sample.

[0089] The non-scattered light may take a common path with the scattered light. This may be used, for instance, wherein the sample is relatively transparent such that large amounts of light pass through the sample without being scattered. However, the non-scattered light may be guided through a different path than the scattered light, which further forms sample information carrying light after passing the light modulator. Thus, the non-scattered light need not necessarily pass through the sample or through the light modulator. The non-scattered light may be subject to specular reflection(s) in a path through which the non-scattered light is guided. Hence, the non-scattered light may be referred to as being “non-scattered” by the non-scattered light not being scattered by the sample even though the non-scattered light may be subject to reflection scattering, e.g. by mirrors along a path of the nonscattered light.

[0090] The imaging device may thus for instance provide in-line digital holography (wherein the non-scattered light travels along a common path with light that interacts with the sample) or provide off-axis holography (wherein the non-scattered light is guided through a different path than the light that interacts with the sample).

[0091] According to an embodiment, the light source is configured to illuminate the sample with a wavelength of light for inducing fluorescence by the sample for forming the scattered light.

[0092] Thus, the light may be scattered by the sample through fluorescence. The scattered light (fluorescent light) passes through the light modulator for modulating the fluorescent light. The light modulator may thus be configured to shape a point spread function of the fluorescent light output by a fluorescent particle.

[0093] In particular, the light modulator may facilitate detecting high spatial frequency components of the fluorescent light by ensuring that an angular direction of the high spatial frequency components is adapted to an acceptance angle of the light-sensitive elements. Thus, the imaging device may facilitate high resolution and high quality imaging of fluorescent particles.

[0094] According to an embodiment, the light modulator is configured to be controlled to compensate for undesired diffraction of light.

[0095] Unwanted objects may cause undesired diffraction of light. Unwanted objects may be in a path of light that is used for imaging of the sample. Thus, light may be diffracted by such unwanted objects before or after interacting with the sample. The objects may be unwanted in terms of not being desired to be imaged even though the objects may form a function in the imaging device (such as holding the sample in an imaging position). The objects may also be unwanted in that the objects may not provide any function in the imaging device and only form an artifact in imaging.

[0096] Undesired diffraction of light may also or alternatively be caused by variations in refraction index in an environment, such as by turbulent air flow.

[0097] The light modulator may be controlled such that an impact by the undesired diffraction of light may be compensated. This may ensure that noise is removed or reduced such that high quality imaging may be performed.

[0098] According to a second aspect, there is provided a method for imaging of a sample by an imaging device, said method comprising: illuminating the sample by a light source of the imaging device for forming scattered light being elastically or inelastically scattered by the sample; modulating the scattered light by a light modulator of the imaging device, and outputting sample information carrying light by the light modulator; detecting a plurality of sample representations based on the sample information carrying light being incident on a plurality of light-sensitive elements of an image sensor of the imaging device; operating the imaging device in a first mode and a second mode, wherein the imaging device is tuned between the first mode and the second mode for tuning an impact of the light modulator on the scattered light, wherein the imaging device applies a first setting in the first mode and a second setting in the second mode, the second setting being different from the first setting, and wherein the image sensor detects the plurality of sample representations by detecting a first sample representation of the plurality of sample representations in the first mode and detecting a second sample representation of the plurality of sample representations in the second mode.

[0099] According to an embodiment of the second aspect, there is provided a method for imaging of a sample by an imaging device, said method comprising: illuminating the sample by a light source of the imaging device for forming scattered light being elastically or inelastically scattered by the sample; modulating the scattered light by a light modulator of the imaging device for altering an angular relation between angular propagation direction within the scattered light and spatial frequency information of the sample carried by the scattered light, and outputting sample information carrying light by the light modulator; detecting a plurality of sample representations based on the sample information carrying light being incident on a plurality of lightsensitive elements of an image sensor of the imaging device; operating the imaging device in a first mode and a second mode, wherein the imaging device is tuned between the first mode and the second mode for tuning an impact of the light modulator on the scattered light, wherein the imaging device applies a first setting in the first mode and a second setting in the second mode, the second setting being different from the first setting, wherein the light modulator outputs sample information carrying light with different angular relations in the first and second modes and alters the angular relation of the scattered light in at least one of the first and the second modes, and wherein the image sensor detects the plurality of sample representations by detecting a first sample representation of the plurality of sample representations in the first mode and detecting a second sample representation of the plurality of sample representations in the second mode.

[0100] Effects and features of this second aspect are largely analogous to those described above in connection with the first aspect. Embodiments mentioned in relation to the second aspect are largely compatible with the first aspect.

[0101] Hence, thanks to the method comprising modulating of scattered light by a light modulator, the method enables scattered light to be controlled such that high frequency components may be detected. In other words, the method facilitates detection of high spatial frequency components of scattered light scattered by the sample. This implies that high resolution imaging may be provided based on detection of the scattered light being modulated by the light modulator.

[0102] Brief description of the drawings

[0103] The above, as well as additional objects, features, and advantages of the present description, will be better understood through the following illustrative and non-limiting detailed description, with reference to the appended drawings. In the drawings like reference numerals will be used for like elements unless stated otherwise.

[0104] Fig. 1 is a schematic view of an imaging device according to a first embodiment.

[0105] Fig. 2 is a schematic view of a light modulator according to an embodiment.

[0106] Figs 3a-3c are schematic views of a light modulator according to another embodiment illustrating control of modulation by the light modulator.

[0107] Figs 4a-4b are schematic views of a light modulator according to yet another embodiment illustrating control of modulation by the light modulator.

[0108] Fig. 5 is a schematic view of an imaging device according to a second embodiment.

[0109] Fig. 6 is a schematic view of an imaging device according to a third embodiment.

[0110] Figs 7a-7b are schematic views of a light modulator according to yet another embodiment illustrating control of modulation by the light modulator.

[0111] Fig. 8 is a flow chart of a method according to an embodiment.

[0112] Detailed description

[0113] Referring now to Fig. 1 , an imaging device 100 according to a first embodiment will be described. The imaging device 100 is described in relation to holographic imaging of a sample, wherein an interference pattern based on light interacting with the sample and light that has not interacted with the sample is acquired. Although reference is made to holographic imaging, it should be realized that the imaging device 100 is not limited to solely being used for holographic imaging and other types of imaging are possible, as will also be exemplified below.

[0114] The imaging device 100 comprises a light source 102. The light source 102 is configured to output light for illuminating a sample 10. The light source 102 may define a location at which light is output. The light source 102 may thus be formed by an optical fiber or waveguide that outputs the light towards the sample 10 and thus forms a source of light for illuminating the sample 10. The light source 102 may comprise a source for generating the light. However, it should be realized that the source for generating the light may alternatively be external to the imaging device 100. The light source 102 may be configured to output light generated by a light-emitting diode (LED) or a laser providing. The light used for illuminating the sample 10 may be at least partially coherent light for allowing holographic imaging.

[0115] The light source 102 is configured to illuminate the sample 10. The sample 10 interacts with illumination light such that light is elastically or inelastically scattered by the sample 10. Below, the imaging device 100 will be mainly described based on elastic scattering by the sample 10, which may be used for holographic imaging of the sample 10.

[0116] The sample 10 may for instance comprise particles to be imaged, such as a biological sample comprising particles in a liquid solution. The scattering of light by the sample 10 may be dependent on shapes of the particles such that the scattered light may carry information relating to the shapes of the particles so as to image the particles of the biological sample. It should be realized that many other types of samples may be imaged by the imaging device 100.

[0117] The imaging device 100 may comprise a receiver structure 120 configured to receive the sample 10 to be imaged. The receiver structure 120 may be configured to control that the sample 10 to be imaged is properly placed for being illuminated by the light source 102 and being imaged by the imaging device 100. Thus, the receiver structure 120 may for instance define a recess in which the sample 10 to be imaged may be placed, such as a recess formed to receive a slide holding the sample 10 to be imaged.

[0118] The imaging device 100 further comprises a light modulator 110. The light modulator 110 may be arranged to receive the scattered light from the sample 10. The light modulator 110 is configured to spatially modulate the scattered light from the sample 10. The scattered light may propagate through the light modulator 110 while being modulated by the light modulator 110. The light modulator 110 may thus affect the scattered light. The light having passed the light modulator 110 may be referred to herein as sample information carrying light.

[0119] The modulation of light provided by the light modulator 110 may be viewed as affecting a light wavefront of the scattered light. In particular, the modulation of light may cause propagation direction of different parts of the light wavefront to be changed. The propagation of light may be viewed as having a main propagation axis at a center of light propagation. Thus, different portions of the scattered light propagate in different directions forming different angles to the main propagation axis. The light modulator 110 is configured to modulate the light wavefront such that propagation directions of light within the wavefront are changed.

[0120] The scattered light may carry spatial frequency information relating to the sample. As mentioned, different portions of the scattered light propagate in different directions forming different angles to the main propagation axis. Information of the sample relating to high spatial frequency may propagate at a larger angle in relation to the main propagation axis compared to information of the sample relating to a low spatial frequency. Thus, the light modulator being configured to modulate the scattered light may provide a redistribution of angular propagation direction of light within the scattered light such that propagation direction of spatial frequency information is altered by the light modulator 110.

[0121] The imaging device 100 further comprises an image sensor 130. The image sensor 130 may be configured to receive the sample information carrying light that has passed the light modulator 110. The image sensor 130 may comprise a plurality of light-sensitive elements 132 arranged in a plane, defining an image plane of the imaging device 100. The light modulator 110 may be configured to spatially modulate light from the sample 10 so as to shape a light pattern in the image plane.

[0122] The image sensor 130 may be any sensor being able to detect and form a representation of incident light. The light-sensitive elements 132 of the image sensor 130 may be arranged in a regularly ordered array. The image sensor 130 may for instance be formed by a complementary metal-oxide- semiconductor (CMOS) sensor or a charge-coupled device (CCD) sensor. Each light-sensitive element 132 is configured to generate a signal representative of intensity of light incident onto the light-sensitive element 132.

[0123] Each light-sensitive element 132 may be configured to detect light that is incident onto the light-sensitive element 132 within a critical acceptance angle in relation to a normal to a surface of the light-sensitive element 132. The critical acceptance angle may be related to a ratio of width of the lightsensitive element 132 and depth of the light-sensitive element 132. The critical acceptance angle may also be related to any lenses or other light guiding elements arranged in relation to each of the light-sensitive elements 132 if such are used. However, since such additional lens or other light guiding elements may in practice anyway not improve the critical acceptance angle very much, the imaging device 100 may preferably not comprise any such additional lens or other light guiding elements.

[0124] The imaging device 100 may further be configured to ensure that light that is incident onto the image sensor 130 at an angle larger than the critical acceptance angle is not detected in order to avoid crosstalk between lightsensitive elements 132.

[0125] The imaging device 100 may be configured such that the normal to the surface of the light-sensitive element 132 may coincide with the main propagation axis of scattered light. However, it should be realized that it is not strictly necessary that the imaging device 100 has such relation between the main propagation axis of scattered light and the normal to the surface of the light-sensitive element 132.

[0126] The light modulator 110 may be configured to alter the relation between the angular propagation direction of light and spatial frequency information of the sample such that portions of light that would otherwise not propagate within the critical acceptance angle is diverted so as to propagate within the critical acceptance angle. Thus, the light modulator 110 may be used for ensuring that the imaging device 100 may detect high spatial frequency information of the sample 10.

[0127] The imaging device 100 is configured such that an interference pattern may be formed between light being scattered by the sample 10 and nonscattered light. The non-scattered light may be formed by light being guided to propagate through a different path so as not to pass the sample 10, wherein the sample information carrying light (based on scattered light) and the non-scattered light may then be combined before being detected by the image sensor 130. However, it should be realized that, in particular if the sample 10 is mainly transparent, the non-scattered light may be formed by light that passes unaffected by the sample 10.

[0128] The interference pattern formed between scattered light and nonscattered light represents information about the sample 10. In particular, the interference pattern may represent holographic imaging of the sample 10. Hence, the imaging device 100 need not include any imaging lens, such that the image sensor 130 may not immediately form a visually understandable image of the sample 10 but may rather detect an interference pattern as a representation of the sample 10. The interference pattern may then be used for reconstructing a visual image representation of the sample 10, if such visual image representation is desired or needed.

[0129] The imaging device 100 is configured to be tuned between at least a first mode and a second mode. The impact of the light modulator 110 on the scattered light received by the light modulator 110 is different between the first mode and the second mode.

[0130] The imaging device 100 may be configured to tune characteristics of the light that illuminates the sample 10, such as tuning the wavelength or polarization of light or a spatial position from which the light is output by the light source 102. The light modulator 110 may be configured to apply a modulation which is dependent on characteristics of light such that tuning of characteristics of light also implies that the impact of the light modulator 110 will change. In such case, a passive light modulator 110 may be used, wherein characteristics of the light modulator 110 may not be dynamically changed.

[0131] The imaging device 100 may also or alternatively be configured to tune the light modulator 110 for changing characteristics of the light modulator 110 so as to change the impact of the light modulator 110 on the received scattered light. The light modulator 110 may thus be configured to be tuned between the first and the second mode of the imaging device 100, wherein different settings of the light modulator 110 in the first mode and the second mode provide different relations of the sample information carrying light between the angular propagation direction of light and spatial frequency information of the sample in the first mode and in the second mode.

[0132] The imaging device 100 may further comprise a controller 140. The controller 140 may be configured to control the light source 102 and / or the light modulator 110 so as to set the mode of the imaging device 100. The controller 140 may be configured to determine settings of the imaging device 100 to be used for controlling the mode of the imaging device 100. The controller 140 may store settings of the imaging device 100 such that settings to be used may be fetched from pre-determined information.

[0133] The imaging device 100 is configured to be apply different settings in the different modes. The light modulator 110 is configured to output sample information carrying light, wherein the relations between the angular propagation direction of light and spatial frequency information of the sample is different in the different modes of the imaging device 100. This implies that the imaging device 100 may be set such that a plurality of sample representations may be detected by the image sensor 130, wherein each sample representation is detected in a respective mode of the imaging device 100.

[0134] The plurality of sample representations may be used in different manners as will be elaborated on below. For instance, the plurality of sample representations may be used for forming combined information for imaging of the sample 10. The image sensor 130 may for instance detect different spatial frequency components of the sample 10 in different sample representations. Thus, the plurality of sample representations may together provide accurate information relating to the sample 10 which may be used for reconstructing a high resolution visual representation of the sample 10.

[0135] As indicated above, the imaging device 100 may be set in at least one of the modes to apply modulation by the light modulator 110 of the scattered light such that spatial frequency information of the scattered light is altered such that at least high spatial frequency content is directed from a first angle to a second angle in relation to a main propagation direction of the scattered light, wherein the second angle is smaller than the first angle. Thus, the imaging device 100 may ensure that high spatial frequency content is detected in the second sample representation detected by the image sensor 130 in the second mode of the imaging device 100.

[0136] The imaging device 100 may further comprise a processing unit 150. The processing unit 150 may be configured to receive the sample representations of intensity of light incident on the array of light-sensitive elements 132 as detected by the image sensor 130. The processing unit 150 may be configured to process the sample representations received from the image sensor 140 so as to reconstruct a visual image of the sample 10. The processing unit 150 may be implemented as a general-purpose processing unit and the imaging device 100 may further comprise a computer program product comprising computer-readable instructions such that when executed on the processing unit 150 the computer program product will cause the processing unit 150 to form a reconstruction of the visual image of the sample 10. In addition, the controller 140 may also be implemented in the same or another general-purpose processing unit the imaging device 100 may further comprise a computer program product comprising computer- readable instructions such that when executed on the general-purpose processing unit the computer program product will cause the general-purpose processing unit to control the imaging device 100 to be set to a desired mode.

[0137] However, the processing unit 150 and / or the controller 140 may alternatively be implemented as firmware arranged, e.g., in an embedded system, or as a specifically designed processing unit, such as an Application- Specific Integrated Circuit (ASIC) or a Field-Programmable Gate Array (FPGA).

[0138] The processing unit 150 may be configured to reconstruct the visual image of the sample 10 by taking into account the respective modulation performed by the light modulator 110 used when acquiring the plurality of sample representations.

[0139] The imaging device 100 may be configured to detect more than two sample representations, wherein each sample representation is acquired using individual unique settings of the imaging device 100. The processing unit 150 may then be configured to reconstruct the visual image based on more than two sample representations, which may allow for reconstructing a high resolution visual representation of the sample 10.

[0140] The processing unit 150 may be part of the imaging device 100 and may be arranged in a physical housing 122 together with other parts of the imaging device 100. However, it should be realized that the imaging device 100 may alternatively be configured to acquire sample representations by the image sensor 130 and may further be configured to transmit such representations to a processing unit being external to the imaging device 100.

[0141] It should also be realized that a visual image need not necessarily be formed at all. The imaging device 100 may be used for analysis of a sample 10, wherein forming of a visual image of the sample 10 may not be strictly necessary. Rather, the sample representations acquired by the image sensor 130 may be directly processed in order to analyze the sample 10. As mentioned above, the plurality of sample representations acquired in different modes of the imaging device 100 may be used for reconstructing a visual image of the sample 10. However, the sample representations may also or alternatively be used in other manners.

[0142] The imaging device 100 may be configured to acquire a first sample representation in the first mode which may then be used for controlling acquisition of sample representation in the second (and further) modes. It should also be realized that the imaging device 100 may be configured to acquire more than one sample representations that are later used for controlling acquisition of further sample representations. Thus, even though reference is made herein to control based on a first sample representation, such control may alternatively be provided based on two or more sample representations, which may be acquired using different settings of the imaging device 100 for each of the sample representations.

[0143] The light modulator 110 may be set in the first mode of the imaging device 100 such that a unitary response is provided by the light modulator 110 to scattered light. Hence, the light modulator 110 may not alter any angular relation of the scattered light in the first mode. For instance, the light modulator 110 may be set such that the light modulator 110 in the first mode is transparent to the received scattered light.

[0144] The light modulator 110 may be set to provide the unitary response by tuning the light modulator 110. However, according to an alternative, the light source 102 may be tuned, for instance by tuning the wavelength of light to a wavelength for which the light modulator 110 is transparent.

[0145] The imaging device 100 may be configured to perform reconstruction based on the interference pattern acquired in the first mode. Thus, the imaging device 100 may be configured to perform conventional holographic reconstruction of a visual image of the sample 10 based on the interference pattern acquired in the first mode. Since the light modulator 110 does not provide any effect based on providing a unitary response, the light modulator 110 need not be taken into account when performing the holographic reconstruction.

[0146] The imaging device 100 may thus be configured to determine a coarse reconstruction of the sample 10 based on the first sample representation. The coarse reconstruction may be relatively quickly determined and may thereafter be used for controlling further acquisition of sample representations such that efficient acquisition of sample information may be achieved. For instance, the coarse reconstruction may control settings used for acquisition of sample representations that allow high resolution imaging of the sample 10. The imaging device 100 may use the coarse reconstruction to control a number of sample representations being acquired with different light modulator settings. This may allow the number of sample representations being acquired to be optimized to a desired resolution. By reducing a number of sample representations being acquired, a speed of acquiring the information needed for high resolution imaging of the sample may be improved. Also, a reduced number of sample representations may imply that reduced processing resources may be needed for image reconstruction.

[0147] Different types of samples may set different requirements of the imaging, e.g., in terms of signal-to-noise ratio and resolution. The imaging device 100 may thus adapt modulation patterns being used for enabling the imaging device 100 to be adapted to imaging of different types of samples. The modulation patterns may involve the modulation performed in a single acquisition of a sample representation but may also involve the different modulations performed in a set of sample representations to be used for acquiring of the plurality of sample representations for desired quality of imaging of the sample 10.

[0148] Thus, the coarse reconstruction may for instance be used for determining the type of sample which may then be used for adapting the modulation pattern to be provided by the light modulator 110.

[0149] In addition, the imaging device 100 may be configured to control further settings of the imaging device 100 based on a first sample representation. For instance, the imaging device 100 may be configured to identify regions of interest in the sample 10 such that further processing may be limited to regions of interest. This may for instance be used such that the information is only extracted from a part of the image sensor 130 such that the further sample representations only represent regions of interest. This may allow speeding up acquisition speed for acquiring the sample representations and processing speed for processing the sample representations.

[0150] The imaging device 100 may store settings to be used by the light modulator 110. Thus, the controller 140 may identify the settings to be used based on the coarse reconstruction and may simply fetch prestored settings to be used for acquisition of further sample representations. Now, the light modulator according to a few different embodiments will be further described in detail. The light modulator of any of these embodiments may be used with the imaging device 100 described above.

[0151] The light modulator 110 may be configured to apply a spatial modulation of light. The spatial modulation may occur based on interaction between the light modulator 110 and light, which may involve absorption, refraction and / or scattering of light. The interaction between the light modulator 110 and light may be dependent on a characteristic of light, such as wavelength or polarization of light.

[0152] The light modulator 110 may be configured to provide a phase and / or amplitude mask of light passing through the light modulator for spatially shaping the light.

[0153] The imaging device 100 may be configured to alter an impact of the modulation by the light modulator 110. This may be used for providing a diversity of imaging which may be utilized in improving reconstruction of a visual image of the sample 10 to be imaged.

[0154] According to an embodiment, the light modulator 110 may be static, whereas the light source 102 may be changed so as to change the impact of the light modulator.

[0155] Referring now to Fig. 2, the light modulator 210 according to an embodiment is shown. The light modulator 210 may comprise scatterers 212, 214 of at least two different types. A first type of scatterer 212 may be configured to be transparent to a first wavelength while being configured to significantly absorb a second wavelength. A second type of scatterer 214 may be configured to significantly absorb the first wavelength while being configured to be transparent to the second wavelength. Thus, by tuning the light source between outputting the first wavelength and outputting the second wavelength, the response of the light modulator 210 may be altered in relation to the distribution of the first type of scatterers 212 and the second type of scatterers 214 in the light modulator 210.

[0156] Hence, the impact of the light modulator 210 for affecting the received scattered light from the sample 10 may be controlled by controlling the wavelength of the light source.

[0157] It should be realized that interaction with light by the scatterers 212, 214 of the at least two different types may depend on polarization instead of wavelength. Thus, first scatterers 212 and second scatterers 214 may align at different directions within the light modulator 210 in order to provide different responses based on light being polarized at different angles. Thus, by tuning the light source 102 between outputting light with a first polarization angle and outputting light with a second polarization angle, the response of the light modulator 210 may be altered in relation to the distribution of the first type of scatterers 212 and the second type of scatterers 214 in the light modulator 210.

[0158] A single control signal may be provided to the light source 102 for controlling wavelength and / or polarization of light. The impact of the control signal may affect the light modulating property of all the scatterers in the light modulator 210.

[0159] Referring now to Figs 3a-3c, a light modulator 310 according to another embodiment will be described. The light modulator 310 comprises at least a first material 312 and a second material 314. The first material 312 and the second material 314 may be arranged forming an interface 316 between the materials in the light modulator 310. The first and the second material may have different optical properties, such as different refractive indices.

[0160] A control signal may be applied to the light modulator 310. The control signal may then be configured to alter a shape of the interface 316, e.g., at a micrometer scale of the interface 316. Thus, when the control signal is applied, the interface 316 will change so as to alter the effect of the light modulator 310 on light changing the impact of modulation.

[0161] Figs 3a-c illustrate schematically how the interface 316 may be changed in dependence of a control signal, wherein Fig. 3a illustrates the interface 316 when no control signal is applied, Fig. 3b illustrates the interface 316 when a first control signal is applied and Fig. 3c illustrates the interface 316 when a second control signal is applied.

[0162] The control signal may for instance be an electrical signal, an acoustic signal, such as an acoustic standing wave, or a thermal signal. The control signal may for instance be applied at a surface of the light modulator 310.

[0163] The impact of the light modulator may alternatively be tuned by tuning the optical property of one or more materials of the light modulator instead of tuning an interface between two materials. Thus, the light modulator may comprise at least two materials with different optical properties, wherein the two materials are arranged within the light modulator in different layers or intermixed with each other. The optical properties of the materials may be changed in dependence of a control signal so as to alter the impact of the light modulator. An effect of the control signal on the optical property may be different for different materials, such that the impact of the light modulator on light is dependent on the control signal. Again, the control signal may for instance be an electrical signal, an acoustic signal, such as an acoustic standing wave, or a thermal signal. When the control signal is applied, an optical property, such as a refractive index, change in a different manner for the first material and the second material of the light modulator so as to change the modulation provided by the light modulator.

[0164] Referring now to Figs 4a-4b, a light modulator 410 according to yet another embodiment will be described. The light modulator 410 comprises particles 412 (or alternatively droplets) arranged within a medium 414, such as a liquid. The particles 412 and the medium 414 have different optical properties, such as different refractive indices.

[0165] A control signal may be applied to the light modulator 410. The control signal may then be configured to alter a distribution of the particles 412 in the medium 414. Thus, when the control signal is applied, the distribution of particles 412 will change so as to alter the effect of the light modulator 410 on light changing the impact of modulation.

[0166] Figs 4a-b illustrate schematically how the distribution of particles 412 may be changed in dependence of the control signal, wherein Fig. 4a illustrates a first distribution when a first control signal (or no control signal) is applied, and Fig. 4b illustrates a second distribution when a second control signal is applied.

[0167] The control signal may for instance be an electrical signal, an electromagnetic signal, such as an electro-magnetic wave, an acoustic signal, such as an acoustic standing wave, or a magnetic field signal. The control signal may for instance be applied at a surface of the light modulator 410.

[0168] The light modulator 210, 310, 410 of any of the embodiments described above may enable a very high resolution of spatial modulation. Spatial modulation may be provided by features of the light modulator 210, 310, 410 that are very small, wherein the features may be provided by individual scatterers / particles in the light modulator or by a spatial variation of a property of the light modulator (such as a variation in the interface between two materials). The features may thus enable a varying light modulating property of the light modulator to be provided. The light modulator 210, 310, 410 may be configured such that each feature affecting light propagation in the light modulator 210, 310, 410 need not be individually addressed, while allowing high resolution features to be involved in the modulation provided by the light modulator 210, 310, 410. Thus, the control signal or the tuning of the emitted light from the light-emitting elements may be configured to control the light modulating property of a plurality of features of the light modulator 210, 310, 410. This enables control of the light modulator 210, 310, 410 using a high resolution.

[0169] According to an embodiment, the features defining a spatial variation of the light modulation may have a size smaller than 10 pm. This enables providing a high spatial resolution of the light modulation. According to another embodiment, the features defining a spatial variation of the light modulation may have a size smaller than a wavelength of the light being modulated by the light modulator 210, 310, 410. This may provide an extremely high spatial resolution of controlling the light modulator 210, 310, 410.

[0170] The light modulator 210, 310, 410 may comprise a large plurality of features that may not be individually controlled for controlling the modulation of light by the light modulator 210, 310, 410. The light modulator 210, 310, 410 should however provide a repeatable transfer function such that the modulation provided by the light modulator 210, 310, 410 by the control signal or by the tuning of the light output by the light source 102 may be predicted.

[0171] Referring now to Fig. 5, the light modulator 110 may be configured to be controlled to compensate for undesired diffraction of light.

[0172] Unwanted objects may cause undesired diffraction of light. Unwanted objects may be in a path of light that is used for imaging of the sample. Thus, light may be diffracted by such unwanted objects before or after interacting with the sample. The objects may be unwanted in terms of not being desired to be imaged even though the objects may form a function in the imaging device (such as the receiver structure 120 holding the sample in an imaging position as shown in Fig. 5). The objects may also be unwanted in that the objects may not provide any function in the imaging device and only form an artifact in imaging.

[0173] Undesired diffraction of light may also or alternatively be caused by variations in refraction index in an environment, such as by turbulent air flow. Thus, the undesired diffraction is not necessarily caused by an object. The light modulator 110 may be controlled such that an impact by the undesired diffraction of light may be compensated. This may ensure that noise is removed or reduced such that high quality imaging may be performed.

[0174] Thanks to the light modulator 110 providing a compensation of the undesired diffraction of light, the sample representations acquired do not include such undesired diffraction. This may ensure that processing time for reconstructing a visual image of the sample 10 may be improved as there may not be a need for processing the sample representations for removing impact of the undesired diffraction of light after the sample representations have been acquired.

[0175] Although the imaging device 100 is described above as being directed to provide holographic imaging of a sample 10, it should be realized that the imaging device 100 may instead be used for fluorescence imaging, as illustrated in Fig. 6.

[0176] The light source 102 may then be configured to illuminate the sample 10 with a wavelength of light for inducing fluorescence by the sample 10 for forming the scattered light.

[0177] Thus, the light may be scattered by the sample 10 through fluorescence. The light modulator 110 may thus be configured to modulate scattered light being fluorescent light. The light modulator may shape a point spread function of the fluorescent light output by a fluorescent particle.

[0178] In particular, the light modulator 110 may facilitate detecting high spatial frequency components of the fluorescent light by ensuring that an angular direction of the high spatial frequency components is adapted to an acceptance angle of the light-sensitive elements 132.

[0179] The imaging device 100 may be set to acquire sample representations in at least two modes. The light modulator 110 may be configured to provide modulation such that different spatial frequency components of the fluorescent light may be acquired in different modes. Thus, the imaging device 100 may facilitate high resolution and high quality imaging of fluorescent particles.

[0180] The imaging device 100 may also be configured to allow both holographic imaging and fluorescence imaging. Thus, the imaging device 100 may be configured to be controlled in order to adapt the light modulator 110 to fit the scattered light being received in dependence on whether the imaging device 100 is used for holographic imaging or for fluorescence imaging. Although it is described above that the light modulator is used for altering an angular relation between an angular propagation direction within the scattered light and spatial frequency information of the sample, the light modulator may alternatively be tuned between different modes for providing different types of imaging.

[0181] Thus, the imaging device may be configured to be controlled in the first mode to provide holographic imaging and may be controlled in the second mode to provide fluorescence imaging. This may imply that the light source 102 may be controllable so as to adapt illumination of the sample for holographic imaging and for fluorescence imaging, respectively. For instance, a wavelength of light output by the light source 102 may be tuned.

[0182] Referring now to Figs 7a-b, a light modulator 510 according to an embodiment for allowing the imaging device 100 to be tuned between holographic imaging and fluorescence imaging will be described.

[0183] The light modulator 510 comprises a non-uniform optical layer 512. The non-uniform optical layer 512 comprises a surface on which scattered light from the sample is incident. The surface is provided with features 514, such as small indentations or projections. These features 514 provide a non- uniform interaction with light across an area of the surface. This may be used for shaping a point spread function of fluorescence light from a sample.

[0184] The light modulator 510 further comprises a second layer 516 being arranged in parallel with the non-uniform optical layer 512 defining a gap 518 therebetween. The second layer 516 may have smooth opposite surface, such that light incident on the second layer 516 will be uniformly affected across an area of the second layer 516.

[0185] In the first mode of the light modulator 510 illustrated in Fig. 7a, the gap 518 may be filled with a refractive index matching medium. This may be a fluid, such as a liquid. For instance, the gap 518 may be connected to a microfluidic system allowing control of filling of the gap 518. The refractive index matching medium may have a same refractive index as the non-uniform optical layer 512 (and the second layer 516). This implies that the light modulator 510 may, in the first mode, provide a unitary response, facilitating detection of a holographic image of the sample.

[0186] In the second mode of the light modulator 510 illustrated in Fig. 7b, the gap 518 may be emptied. Thus, the gap 518 may be filled with air. Alternatively, the gap 518 may be filled with another medium having a different refractive index from the non-uniform optical layer 512. This implies that the features of the non-uniform optical layer 512 provide a modulation of scattered light from the sample, wherein the scattered light is fluorescent light. The light modulator may shape a point spread function of the fluorescent light output by a fluorescent particle.

[0187] Referring now to Fig. 8, a method for imaging will be briefly summarized. The method may be used by any of the embodiments of the imaging device 100 described above.

[0188] The method comprises illuminating 702 the sample by a light source of the imaging device for forming scattered light being elastically or inelastically scattered by the sample.

[0189] The method further comprises modulating 704 the scattered light by a light modulator of the imaging device for altering an angular relation between angular propagation direction within the scattered light and spatial frequency information of the sample carried by the scattered light, and outputting sample information carrying light by the light modulator. The light modulator may thus receive scattered light from the sample and may output sample information carrying light wherein the received scattered light has been modulated.

[0190] The method further comprises detecting 706 a plurality of sample representations based on the sample information carrying light being incident on a plurality of light-sensitive elements of an image sensor of the imaging device.

[0191] The method further comprises operating the imaging device in a first mode and a second mode, wherein the imaging device is tuned between the first mode and the second mode for tuning an impact of the light modulator on the scattered light, wherein the imaging device applies a first setting in the first mode and a second setting in the second mode, the second setting being different from the first setting. The light modulator outputs sample information carrying light with different angular relations in the first and second modes and alters the angular relation of the scattered light in at least one of the first and the second modes. The image sensor detects the plurality of sample representations by detecting a first sample representation of the plurality of sample representations in the first mode and detecting a second sample representation of the plurality of sample representations in the second mode.

[0192] The plurality of sample representations may be used in combination for reconstructing a visual image of the sample with high resolution. Also or alternatively, the first sample representation may be used for controlling second (and further) sample representations to be acquired. In the above the inventive concept has mainly been described with reference to a limited number of examples. However, as is readily appreciated by a person skilled in the art, other examples than the ones disclosed above are equally possible within the scope of the inventive concept, as defined by the appended claims.

Claims

CLAIMS1 . An imaging device (100) for imaging of a sample (10), said imaging device (100) comprising: a light source (102) configured to illuminate the sample for forming scattered light being elastically or inelastically scattered by the sample (10); a light modulator (110; 210; 310; 410; 510) configured to receive the scattered light from the sample (10) and configured to modulate the scattered light, wherein the light modulator (110; 210; 310; 410; 510) is configured to output sample information carrying light; and an image sensor (130) comprising a plurality of light-sensitive elements (132), wherein each light-sensitive element (132) is configured to generate a signal representative of intensity of light incident onto the light-sensitive element (132), wherein the image sensor (130) is configured to detect a plurality of sample representations based on the sample information carrying light being incident on the plurality of light-sensitive elements (132); wherein the imaging device (100) is configured to be tuned between at least a first mode and a second mode for tuning an impact of the light modulator (110; 210; 310; 410; 510) on the received scattered light, wherein the light modulator (110; 210; 310; 410; 510) is configured to present features (212, 214; 316; 412, 414; 514) defining a variable light modulating property in a cross-section of the light modulator (110; 210; 310; 410; 510) perpendicular to a main propagation direction of the scattered light, wherein the imaging device (100) is configured to apply a first setting in the first mode and a second setting in the second mode, the second setting being different from the first setting; and wherein the plurality of sample representations comprise a first sample representation detected for the first mode of the imaging device (100) and a second sample representation detected for the second mode of the imaging device (100).

2. The imaging device according to claim 1 , wherein the light modulator is configured to modulate the scattered light for altering an angular relation between angular propagation direction within the scattered light and spatial frequency information of the sample carried by the scattered light, and , wherein the light modulator is configured to output sample informationcarrying light with different angular relations in the first and second modes.

3. The imaging device according to claim 2, wherein the imaging device is configured to control impact of the light modulating property on the received scattered light using a single signal for controlling impact of the light modulating property of a plurality of features.

4. The imaging device according to claim 2 or 3, wherein the features (212, 214; 316; 412, 414) defining the variable light modulating property have a size smaller than 10 pm, such as smaller than a wavelength of the scattered light.

5. The imaging device according to any one of claims 2-4, wherein the light modulator (110; 210; 310; 410) is configured to, at least in the second mode, apply modulation of the scattered light such that spatial frequency information of the scattered light is altered such that at least high spatial frequency content is directed from a first angle to a second angle in relation to a main propagation direction of the scattered light, wherein the second angle is smaller than the first angle.

6. The imaging device according to any one of the preceding claims, wherein the imaging device (100) is configured to be tuned between more than two modes and configured to apply different settings in different modes, wherein the imaging device (100) is configured to reconstruct a visual image of the sample based on the plurality of sample representations detected for the more than two modes of the imaging device.

7. The imaging device according to any one of claims 2-6, wherein the light modulator (110; 210; 310; 410) is configured in the first mode of the imaging device (100) to provide a unitary response to scattered light such that the light modulator (110; 210; 310; 410) in the first mode of the imaging device (100) does not alter the angular relation.

8. The imaging device according to claim 7, wherein the imaging device (100) is configured to perform coarse reconstruction of the sample (10) based on the first sample representation.

9. The imaging device according to claim 8, wherein the imaging device (100) is configured to use the coarse reconstruction of the sample (10) for controlling a number of sample representations of different light modulator settings to be detected for high resolution reconstruction of the sample (10).

10. The imaging device according to claim 8 or 9, wherein the imaging device (100) is configured to use the coarse reconstruction of the sample (10) for controlling a modulation pattern provided by the light modulator (110; 210; 310; 410).11 .The imaging device according to any one of claims 8-10, wherein the imaging device (100) is configured to use the coarse reconstruction of the sample (10) for controlling settings of the image sensor (130) for detecting the sample representations.

12. The imaging device according to any one of claims 2-11 , wherein the light modulator (110; 210; 310; 410) is configured to, in at least one of the first and the second mode, apply a modulation pattern that is adapted to a type of sample to be imaged, wherein the imaging device (100) is configured to store settings of the light modulator (110; 210; 310; 410) for a plurality of different types of samples.

13. The imaging device according to any one of claims 2-12, wherein the light modulator (110; 210; 310; 410) is configured to be tuned between the first and the second mode of the imaging device (100), wherein different settings of the light modulator (110; 210; 310; 410) in the first mode and the second mode provide different angular relations of the sample information carrying light between the first mode and the second mode.

14. The imaging device according to any one of claims 2-13, wherein the light source (102) is configured to be tuned between the first mode and the second mode of the imaging device (100) such that a characteristic of the illumination light is changed between the first mode and the second mode, wherein the light modulator (110; 210; 310; 410) is configured to alter the angular relation in dependence of the characteristic of illumination light to provide a different angular relation of the sample information carrying lightbetween the first mode and the second mode.

15. The imaging device according to any one of the preceding claims, wherein the image sensor (130) is configured to detect each of the plurality of sample representations as an interference pattern formed at a plane of the image sensor (130) by the sample information carrying light output from the light modulator (110; 210; 310; 410) and non-scattered light from the light source (102).

16. The imaging device according to any one of the preceding claims, wherein the light source (102) is configured to illuminate the sample (10) with a wavelength of light for inducing fluorescence by the sample (10) for forming the scattered light.

17. The imaging device according to claim 1 , wherein the light modulator (510) is configured in the first mode of the imaging device (100) to provide a unitary response to scattered light, wherein the image sensor (130) is configured to detect a holographic image in the first sample representation, and wherein the light modulator (510) is configured in the second mode of the imaging device (100) to provide a shaping of a point spread function, wherein the image sensor (130) is configured to detect a fluorescence image in the second sample representation.

18. The imaging device according to claim 17, wherein the light modulator (510) comprises a non-uniform layer (512) configured to provide the shaping of the point spread function, wherein the light modulator (510) is further controllable in the first mode for arranging a refractive index matching medium in contact with the non-uniform layer (512) for forming a uniform interface.

19. A method for imaging of a sample by an imaging device, said method comprising: illuminating (702) the sample by a light source of the imaging device for forming scattered light being elastically or inelastically scattered by the sample; modulating the (704) scattered light by a light modulator of the imaging device, and outputting sample information carrying light by the lightmodulator; detecting (706) a plurality of sample representations based on the sample information carrying light being incident on a plurality of light-sensitive elements of an image sensor of the imaging device; operating the imaging device in a first mode and a second mode, wherein the imaging device is tuned between the first mode and the second mode for tuning an impact of the light modulator on the scattered light, wherein the imaging device applies a first setting in the first mode and a second setting in the second mode, the second setting being different from the first setting, wherein the image sensor detects the plurality of sample representations by detecting a first sample representation of the plurality of sample representations in the first mode and detecting a second sample representation of the plurality of sample representations in the second mode.

Images