A multichannel imaging device, a multichannel imaging apparatus implementing such multichannel imaging device as well as a computer implemented method for processing image data obtained with such multichannel imaging device
The multichannel imaging device addresses the trade-off in imaging systems by using aligned microlenses and a positioning stage to achieve high-resolution, large FOV, and magnification, ensuring comprehensive sample imaging.
Patent Information
- Application Number
- PCT/EP2025/058989
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-04-12
- Filing Date
- 2025-04-02
- Publication Date
- 2025-10-09
AI Technical Summary
Existing imaging systems face a trade-off between field-of-view (FOV), resolution, and miniaturization, with classical single-channel systems failing to meet the requirements of large FOV and high magnification while being compact enough for integration into platforms like organ-on-a-chip or lab-on-a-chip.
A multichannel imaging device with an array of optical channels, each comprising a first and second microlens and a micro aperture, aligned along a common optical axis, coupled with a composite light-sensitive sensor and an XY-positioning stage, allows for high-resolution imaging with increased FOV and magnification by scanning the sample in both X and Y directions.
The multichannel imaging device achieves a compact design with improved FOV, resolution, and magnification, enabling complete imaging of a sample without interruptions by capturing and stitching images from multiple channels.
Smart Images

Figure EP2025058989_09102025_PF_FP_ABST
Abstract
Description
[0001] TITLE
[0002] A multichannel imaging device, a multichannel imaging apparatus implementing such multichannel imaging device as well as a computer implemented method for processing image data obtained with such multichannel imaging device.
[0003] TECHNICAL FIELD
[0004] The present disclosure relates to image data processing technologies implementing a multichannel imaging device. In particular, this disclosure presents a new design of such multichannel imaging device as well as a sophisticated technique to process large amount image data obtained from imaging a sample.
[0005] BACKGROUND OF THE DISCLOSURE
[0006] A vast number of applications (Live cell imaging, biological applications, hardware inspection, micro-electronics etc.) require imaging systems that can image a large Field of View while retaining resolution in the order of micrometres and offering larger than 1x magnification. Another requirement of the applications is the need of an imaging system that is compact in order to fit in integration platforms like organ-on-a-chip, lab-on-a-chip etc. A classical imaging system comprised by a single optical channel cannot achieve all the previous requirements, since there is a trade-off between field-of-view (FOV), resolution and the miniaturization of optics. A multi-channel imaging system can address the previous challenges (FOV, resolution, compact size) but is generally used in a relay optical setup offering magnification of 1x (or less).
[0007] Accordingly, it is a goal of the present disclosure to provide an improved configuration of a multichannel imaging device of reduced constructional dimensions, yet with an improved optical setup in terms of FOV, resolution, and magnification.
[0008] SUMMARY OF THE DISCLOSURE
[0009] According to a first example of the disclosure, a multichannel imaging device is proposed, at least comprising an array of K_x_L optical channels, with K and L being an integer number of 2 or more, with each optical channel having an entrance and an exit for light impinging on the entrance, as well as a channel optical axis, wherein each optical channel is formed as an ommatidium comprising - seen from the entrance in the direction of the exit - a first microlens element at the entrance, a micro aperture, and a second microlens at the exit. It furthermore includes a composite light sensitive sensor for receiving light exiting from each second microlens element and outputting electric signals representing the light being exited by each second microlens element.
[0010] In particular, for each optical channel, the first microlens element, the micro aperture, and the second microlens have an optical axis which coincides with the channel optical axis of the associated optical channel.
[0011] In a particular advantageous example, the channel optical axes of the array of optical channels extend parallel to each other, such that each optical channel has an unique field of view.
[0012] In an example incorporating a flexible design, the first microlenses may be arranged in a first microlens array, the micro apertures may be arranged in a micro aperture array, and / or the second microlenses may be arranged in a second microlens array.
[0013] In particular, the first microlens elements and / or the second microlens elements have a refractive index of n between 1.4 and 1.6, in particular between 1.49 and 1.50 and in particular n = 1.491756.
[0014] In a further advantageous example of the multichannel imaging device, each microchannel has an outer dimension of X_x_Y mm2and a field of view of X / N_x_Y / N mm2, with N being an integer number of {2, 3, 4, 5, ... , 50-75-100}. In principle, N can take theoretically any integer number (also larger than 100). However, N approaching 100 is considered a good practical end (if needed) as more than 100 magnification will be less feasible.
[0015] As to specific geometrical configurations, the first microlens elements and / or the second microlens elements may have a rectangular or spherical configuration.
[0016] In a further aspect according tot the disclosure, a multichannel imaging apparatus is proposed, which may comprise a light source structured to emit electromagnetic radiation in the visible region of the electromagnetic spectrum towards a mount structured to accommodate a sample to be illuminated by the electromagnetic radiation being emitted by the light source. It incorporates a multichannel imaging device as disclosed in this patent application, which is structured to receive electromagnetic radiation being transmitted through the sample accommodated on the mount. In addition, an XY-positioning stage is implemented, and structured for positioning the mount and / or the multichannel imaging device relative to each other in an XY-plane perpendicular to the propagation direction of the electromagnetic radiation through the multichannel imaging device.
[0017] In order to ascertain a compact and rigid design which is not or less affected by disturbances and vibrations, the apparatus furthermore comprises a mounting frame of accommodating the light source, the mount, the multichannel imaging device and the XY- positioning stage.
[0018] Additionally, a data processing unit is incorporated for receiving and processing the electric signals outputted by the composite light sensitive sensor and generate an image representing the sample being illuminated. Moreover, a storage means or storage unit may be provided of storing each array of images acquired.
[0019] Another aspect of the disclosure pertains to a method for imaging an sample accommodated in a multichannel imaging apparatus according to the disclosure implementing a multichannel imaging device according to the disclosure. As stipulated the multichannel imaging device according to the disclosure has an array of K_x_L optical channels OCk.i, with k e [0, 1 , 2, ..., K-1] and I e [0, 1 , 2, ..., L-1], In particular the array of K_x_L optical channels OCk.i, is arranged in an XY-plane orientation, with the rows K of the array oriented along the Y-direction of the XY-plane orientation, and the columns L of the array being oriented along the X-direction (or X-dimension) of the XY-plane orientation. Furthermore, wherein each microchannel OCk.i has an outer dimension of X_x_Y mm2and a field of view of X / N x Y / N mm2.
[0020] The method comprises the steps of: i) providing a sample in the mount of the multichannel imaging apparatus; ii) performing in both an X-direction and an Y-direction of an XY-plane perpendicular to the propagation direction of the electromagnetic radiation through the multichannel imaging device, using the XY-positioning stage and the multichannel imaging device, a number of n image acquisition sequences ASn, with n e [0, 1 , 2, ..., N-1], with each n image acquisition sequences ASnconsisting of: ii-1) acquiring from the sample and from each optical channel OCk.i of the multichannel imaging device, an array of images I (yn, xn, k, I); ii-2) displacing, using the XY-positioning stage, the multichannel imaging device relative to the mount, over a distance of X / N (Y / N) mm in the X (Y) direction of the XY- plane.
[0021] With this scanning method, the whole sample present in the mount can be imaged without interruptions. By displacing the mount I the multichannel imaging device relative to each other by means of the XY-positioning stage is it possible to capture N2(N times in the X-direction and N times in the Y-direction) captured images in the XY plane. The number of scanning steps N is linearly related to the outer dimension of each individual microchannel and the associated field of view of that microchannel. In case of an outer dimension of X_x_Y mm2and a field of view of X / N_x_Y / N mm2a number of N scans ASnare performed by the multichannel imaging device in both the X-direction and the Y-direction. For each scanning step, the XY-positioning stage displaces the multichannel imaging device relative to the mount, over a distance of X / N mm in the X direction of the XY-plane and subsequently over a distance of X / N mm in the Y direction of the XY-plane.
[0022] Each one of the NxN captured images ASncomprises by K_x_L fields of interest (as there are K_x_L microchannels OCk.i which are used NxN times for image acquisition). The K_x_L fields of interest each have a field of view of X / N_x_Y / N mm2and corresponds to a different microchannel OCk,i. As a result, the total fields of interest in the image acquisition are N2x (K_x_L).
[0023] In a further example, the method further comprises the step of iii) storing, using the storage unit, each array of images l(yn, xn, k, I) acquired with each step ii-1). Accordingly, the array of images can be used at a later stage in order to compose a complete image of the sample.
[0024] It is noted, that it is preferred to position, prior to step i) or step ii), using the XY-positioning stage, the multichannel imaging device relative to the mount at an initial position, such that the microchannel OCo.o is located at the top left part of the total desired FOV. The top left part of the total desired FOV is positioned in the origin (0,0) as defined by the X and Y axes of the XY-plane of the mount on which the sample is deposited for imaging purposes. With this orientation, the OCo.o center is displaced placed X / N units to the right (in the X-direction) and Y / N units downward (in the Y-direction) from the top left corner of the desired FOV.
[0025] BRIEF DESCRIPTION OF THE DRAWINGS
[0026] The disclosure will now be discussed with reference to the drawings, which show in:
[0027] Figures 1a and 1b a general overview and a detail of a multichannel imaging apparatus according to the disclosure incorporating a multichannel imaging device according to the disclosure;
[0028] Figures 2a and 2b a general overview and a detail of a multichannel imaging device according to the disclosure; Figures 3a and 3b further details of a multichannel imaging device according to the disclosure;
[0029] Figure 4 a further example of a multichannel imaging device according to the disclosure;
[0030] Figures 5a-5e details outlining a method according to the disclosure.
[0031] DETAILED DESCRIPTION OF THE DISCLOSURE
[0032] For a proper understanding of the disclosure, in the detailed description below corresponding elements or parts of the disclosure will be denoted with identical reference numerals in the drawings.
[0033] Figure 1a and its detail in Figure 1 b depict a general overview and a detail of a multichannel imaging apparatus according to the disclosure incorporating a multichannel imaging device according to the disclosure. In this application reference numeral 100 relates to the multichannel imaging apparatus, whereas reference numeral 10 is referencing to the multichannel imaging device according to the disclosure.
[0034] As outlined previously, a vast number of applications (Live cell imaging, biological applications, hardware inspection, micro-electronics etc.) require imaging systems that can image a large Field of View while retaining resolution in the order of micrometres and offering larger than 1x magnification. Another requirement of the applications is the need of an imaging system that is compact in order to fit in integration platforms like organ-on-a-chip, lab-on-a-chip etc. A classical imaging system comprised by a single optical channel cannot achieve all the previous requirements, since there is a tradeoff between field-of-view (FOV), resolution and the miniaturization of optics. A multi-channel imaging system can address the previous challenges (FOV, resolution, compact size) but is generally used in a relay optical setup offering magnification of 1x (or less).
[0035] In Figures 1a and 1b, a multichannel imaging apparatus is proposed implementing an improved optical setup in terms of FOV, resolution, and magnification.
[0036] The multichannel imaging apparatus 100 may be composed of a mounting frame 101. The mounting frame can be of any geometrical configuration, yet in this particular example the mounting frame 101 is placed on (supported by) a pedestal 102. The mounting frame 101 - in this particular example - is formed as a support with a guiding system 103 shaped as guiding rails.
[0037] The multichannel imaging apparatus 100 comprises a light source 110 which is structured to emit through a light exit face 111 electromagnetic radiation in the visible region of the electromagnetic spectrum. The light source 110 is mounted to the mounting frame 101 by means of a support 115, which can be accommodated in the guiding rail of the guiding system 103. In particular, a LED light source emitting white light can be used. Alternatively, experiments have shown that a LED light source emitting green light in the 495-570 nm wavelength range show better imaging results since there were fewer chromatic aberrations. In this particular configuration, the light source 110 emits light in a vertical; upwards direction (more or less parallel) to the mounting frame support 101 towards a mount 120. The mount 120 can have any configuration but in a particular example the mount 120 is configured as a sample holder provided with the sample holding area 121 in or at which a sample (not shown) can be accommodated.
[0038] The sample accommodated in the sample holding area 121 is to be illuminated via its bottom side by the electromagnetic radiation being emitted by the light source 110.
[0039] Moreover, the multichannel imaging apparatus 100 incorporates a multichannel imaging device 10 according to the disclosure, its functionality being described below in the detailed description. The multichannel imaging device 10 receives electromagnetic radiation being transmitted through the sample accommodated on the mount 120 (or in the sample holding area 121 of the mount 120). The electromagnetic radiation being received by the multichannel imaging device 10 is magnified and subsequently received by a composite light sensitive sensor 140. Both the multichannel imaging device 10 and the composite light sensitive sensor 140 are mounted to the mounting frame 101 by means of a support 145, which can be accommodated in the guiding rail of the guiding system 103 (in a similar manner as the support 115 of the light source 110).
[0040] Reference numeral 130 denotes an XY-positioning stage which is accommodated in the mount 101. The XY-positioning stage 130 allows a proper positioning of the mount 120 and / or the multichannel imaging device 10 relative to each other in an XY-plane perpendicular to the propagation direction of the electromagnetic radiation through the multichannel imaging device 10. In this example as shown in Figure 1 the propagation direction of the electromagnetic radiation being emitted by the light source 110 is in a vertical Z-direction parallel to the vertical orientation of the mount support 101. The XY-positioning stage 130 is mounted to the mounting frame 101 by means of a support 135, which can be accommodated in the guiding rail of the guiding system 103 (in a similar manner as the supports 115 and 145).
[0041] It should be noted, that due to the orientation of the mounting frame 101 relative to the horizontal, the various components being the light source 110, the XY- positioning stage 130, the mount 120, the multichannel imaging device 10 and the composite light sensitive sensor 140 can be positioned relative to each other along the z- direction of the guiding rail 103 of the mounting support 101 using suitable (quick) release mechanisms which are part of the various supports 115, 135 and 145.
[0042] Thus, the XY-positioning stage 130 is capable of positioning the mount 120 and / or the multichannel imaging device 10 relative to each other in an XY-plane perpendicular to the z-direction of the guiding rail 103 of the mounting support 101.
[0043] The overall construction of the multichannel imaging apparatus 100 according to the disclosure ascertains a compact, yet rigid design which is not or less affected by disturbances and vibrations.
[0044] In Figure 1 b, a data processing unit 150 may be implemented for receiving and processing the electric signals outputted via the signal line 150a by the composite light sensitive sensor 140 and to generate an image representing the sample being illuminated by the light source 110. Additionally, a storage unit 160 can be implemented for storing via the signal line 160a each array of images generated by the data processing unit 150 as well as for retrieving those images back to the storage unit 160 for generating the ultimate composite image representing the sample.
[0045] Figures 2a and 2b and details in Figure 3a and 3b show an example of a multichannel imaging device according to the disclosure. The multichannel imaging device 10 is composed of at least comprising an array of K_x_L optical channels 15. Note that the indices K and L are an integer number of 2 or more. The number of optical channels is q, with q being defined by the product K_x_L. Each optical channel OCk.i, denoted with reference numeral 15q, is shown in Figure 2b and has an entrance 15a and an exit 15b for light impinging on the entrance 15a. Reference numeral 15z denotes a channel optical axis for each optical channel 15q.
[0046] Each optical channel 15qis formed as an ommatidium comprising - seen from the entrance 15a in the direction towards the exit 15b - a first microlens element 11qat the entrance 15a, a micro aperture 12q, and a second microlens 13qat the exit 15b. In particular, the various first microlenses 11qmay be arranged in a first microlens array 1100, the micro apertures 12qmay be arranged in a micro aperture array 1200, and / or the second microlenses 13qmay be arranged in a second microlens array 1300.
[0047] The micro-aperture array 1200 may be comprised by several microapertures 12qhaving constant dimensions, and may have for example a square or a circular form in the array formation. As shown in Figure 2b, each optical channel 15qof the multichannel imaging device 10 is comprised by one micro lens 11qfrom the first microlens array 1100, one micro aperture 12qfrom the micro-aperture array 1200 and one micro lens 13qfrom the second micro-lens array 1300. According to the disclosure, the three components forming an optical channel 15qshare the same optical axis 15z that pass through their center. In particular, for each optical channel 15q, the first microlens element 11q, the micro aperture 12q, and the second microlens 13qhave an optical axis which coincides with the channel optical axis 15z of the associated optical channel 15q.
[0048] In particular and as depicted in Figure 2a, the channel optical axes 15z of the array 1500 of optical channels 15qextend parallel to each other, such that each optical channel 15qhas an unique field of view (FOV).
[0049] The light outputted by the various optical channels 15qis collected by a composite light sensitive sensor 140, structured to receive light exiting from each second microlens element 13qand outputting electric signals representing the light being exited by each second microlens element 13q.
[0050] For each micro channel 15q, the central field (that coincides with the starting point of the respective optical axis 15z) is the point on the object plane 1 that is opposite to the central point of the corresponding micro lens 11qof the first micro-lens array 1100. The FOV of each micro channel 15qis a part of the object 1 that has the same shape as the micro-lenses 11qand has dimensions of for example 1 / 5 of the dimensions of one microlens 11q. Accordingly, In this disclosure, the FOV of each micro channel 15qis formed (centered) around the optical axis 15z and is considered smaller than outer dimensions of the corresponding micro-lens 11q.
[0051] In an example, each micro channel 15qexhibits a magnification of 4x, with a FOV of 0.2 x 0.28 mm2and having an outer dimension, seen perpendicular to the optical axis 15z, of 1 x 1.4 mm2. Thus the FOV is 1 / 5 of the dimensions of the micro channel I micro-lens. In a further example, where the multichannel imaging device has an array of 6 x 6 microchannels 15q, the total FOV of the 36 microchannels will be 6 x 8.4 mm2.
[0052] The first micro lenses 11qimages the FOV of the object 1 on an intermediate image plane where the micro-aperture 12qis positioned. The micro apertures 12qacts as a field stop blocking all rays of the light emitted by the light source 110 that are outside of the FOV of the respective channel 15q. The second microlens 13quses as an object the intermediate image of the micro-aperture 12qand images it on the sensor plane 2 (of the composite light sensitive sensor 140) with a certain magnification.
[0053] It should be noted that the above optical configuration can implement any number of microchannels 15qforming the array 1500. Without loss of generality and with a possible extension or minimization of the number of channels 15q, a simplified example of a multichannel imaging device 10 is depicted in Figure 2a comprising four (K_x_L = 2 x 2) channels.
[0054] As shown in Figure 4, an example comprising four microchannels 15qas an embodiment of the invention. It is apparent that the image 2 on the composite light sensitive sensor 140 is made of several segmented parts of the object 1. Between any two adjacent images on the sensor plane there are parts of the object that are not imaged, which lie on the parts of the object 1 between the FOVs of two adjacent channels.
[0055] This phenomenon is shown by the dark lines of Figures 5A-5E, which depicts an example of K_x_L = 6 x 6 = 36 microchannels 15q.
[0056] It is obvious that different focal lengths, different positions and different dimensions of the optical elements 11q-12q-13qwill produce imaging systems with modified magnification, resolution, optical aberrations and image quality. All of them based on the same imaging principles as presented on this patent application.
[0057] In particular, the first microlens elements 11qand / or the second microlens elements 13qhave a refractive index of n between 1.4 and 1.6, in particular between 1.49 and 1.50 and in particular n = 1.491756. Preferably, the first microlens elements 11qmay have a length dimension (seen along the optical axis 15z) of L1 amounting 1.2 mm and a width dimension D1 of 1 mm. Similarly, the second microlens elements 13qmay have a length dimension (seen along the optical axis 15z) of L2 amounting 1.2 mm and a width dimension D2 of 1 mm.
[0058] As to specific geometrical configurations, the first microlens elements 11qand / or the second microlens elements 13qmay have a rectangular or spherical configuration.
[0059] Another aspect of the disclosure pertains to a method for imaging an sample accommodated in the multichannel imaging apparatus 100 according to the disclosure which implements a multichannel imaging device 10 according to the disclosure. As stipulated the multichannel imaging device 10 according to the disclosure has an array of K_x_L optical channels OCk.i, with k e [0, 1 , 2, ..., K-1 ] and I e [0, 1 , 2, ..., L-1], In particular the array of K_x_L optical channels OCk.i, is arranged in an XY-plane orientation, with the rows K of the array oriented along the Y-direction of the XY-plane orientation, and the columns L of the array being oriented along the X-direction (or X-dimension) of the XY- plane orientation. Furthermore, wherein each microchannel OCk.i has an outer dimension of X_x_Y mm2and a field of view of X / N_x_Y / N mm2. In this particular application of the multichannel imaging device 10, for each micro channel 15q, the central field (that coincides with the starting point of the respective optical axis 15z) is the point on the object plane 1 that is opposite to the central point of the corresponding micro lens 11qof the first micro-lens array 1100. The FOV of each micro channel 15qis a part of the object 1 that has the same shape as the micro-lenses 11qand has dimensions being smaller (for example 1 / 5th) of the dimensions of one micro-lens 11q. Accordingly, the FOV of each micro channel 15qis formed (centered) around the optical axis 15z and is considered smaller than outer dimensions of the corresponding micro-lens 11q.
[0060] In an example which is used purely for clarifying the method of the disclosure, each micro channel 15qexhibits a magnification of 4x, with a FOV of 0.2 x 0.28 mm2and having an outer dimension, seen perpendicular to the optical axis 15z, of 1 x 1.4 mm2. Thus the FOV is 1 / 5 of the dimensions of the micro channel I micro-lens. In a further example, where the multichannel imaging device has an array of 6 x 6 microchannels 15q, the total FOV of the 36 microchannels will be 6 x 8.4 mm2.
[0061] This example of a K_x_L (6_x_6) array of microchannels 15qis depicted in Figures 5A-5E. In order to address the problem, that between two adjacent images on the sensor plane there are parts of the object that are not imaged, which lie on the parts of the object 1 between the FOVs of two adjacent channels, as marked by the dark lines of Figures 5a-5e, the method according to the disclosure provides a solution.
[0062] Next to providing a sample in the sample holding area 121 of the mount 120 of the multichannel imaging apparatus 100, the method furthermore performs, in both an X-direction and an Y-direction of the XY-plane perpendicular to the propagation direction of the electromagnetic radiation through the multichannel imaging device 10, using the XY- positioning stage and the multichannel imaging device, a number of n image acquisition sequences ASn, with n e [0, 1 , 2, ..., N-1],
[0063] As shown in Figure 1 B, the XY-plane is formed by the planar configuration of the mount 120 on which the sample is placed in the sample mounting area 121.
[0064] The various image acquisition sequences ASnare performed with respect to both the X-direction and the Y-direction of the XY-plane formed by the mount. For a proper understanding it is irrelevant, whether the method is performed first with respect to the X- direction and second with respect to the Y-direction of the XY-plane, or the other way around. The various image acquisition sequences ASnmay be performed with respect to the X-direction and subsequent with respect to the Y-direction, or may be performed with respect to the Y-direction first and subsequently with respect to the X-direction. In both situations with respect to the X-direction and the Y-direction of the YX-plane, each n image acquisition sequence ASnis composed of ii-1) acquiring from the sample and from each optical channel OCk.i of the multichannel imaging device, an array of images l(yn, xn, k, I). An example of such array of images is depicted in Figure 5a. Note that:
[0065] • K_x_L is 6_x_6, that is K (6) channels seen along the Y-direction and L (6) channels seen along the X-direction of the XY-plane formed by the mount 120.
[0066] • N = 5, as each individual FOV is 1 / 5 of the dimensions of a micro channel 15q.
[0067] • n e [0, 1 , 2, 3, 4]
[0068] In this particular example, the first image acquisition sequence ASo (n = 0) out of 25 captured images from the scanning procedure is shown. The 36 fields of interest are shown as white rectangles. By performing the forementioned scanning procedure 25 images will be captured.
[0069] The various, 25 images (field of views) l(yn, xn, k, I) captured with each particular the acquisition sequence receive an unique annotation following the format ynxnkl, with:
[0070] • the first digit ynbeing the value of n for the acquisition sequence being performed with respect to the Y-direction
[0071] • the second digit xnbeing the value of n for the acquisition sequence being performed with respect to the X-direction
[0072] • the third digit k with k e [0, 1 , 2, ..., K-1] being the row location of the respective optical channel in the microchannel array oriented along the Y-direction of the XY- plane orientation;
[0073] • the fourth digit I with I e [0, 1 , 2, ..., L-1] being the column location of the respective optical channel in the microchannel array oriented along the X-direction of the XY- plane orientation.
[0074] Accordingly, the first, most top and left image (field of view) is denoted with «0000», representing the first image acquisition performed with respect to both the Y and X direction (ynand xnboth 0) for the optical channel located at the most top first row (k=0) and most left first column (l=0). Likewise, the most bottom and right image (field of view) is denoted with «0055», representing the first image acquisition performed with respect to both the Y and X direction (ynand xnboth 0) for the optical channel located at the most bottom sixth row (k=5) and the most right sixth column (l=5).
[0075] For Figure 5A, the respective images of the various optical channels in the K_x_L microchannel array can be denoted as a matrix shown below: <<0000»<<0001 »<<0002>><<0003>><<0004>>«0005» «0010»«001 1 »«0012»<<0013»«0014»«0015» «0020»<<0021 »<<0022>x<0023>x<0024>><<0025» «0030»<<0031 »<<0032>x<0033>x<0034>><<0035» «0040»<<0041 »<<0042>x<0043>x<0044>><<0045» «0050»<<0051 »<<0052>x<0053>x<0054>><<0055»
[0076] An important note about the image 0000 of Figure 5A is that between each field of interest there is a blind area. In the particular example of each optical channel OCk.i having a FOV of 0.2 x 0.28 mm2and an outer dimension, seen perpendicular to the optical axis 15z, of 1 x 1.4 mm2, between each adjacent field of interest in the x direction there is a 1.12 x 0.8 mm2FOV that is not visible on the image. In order to reveal this blind area, in particular to acquire this blind area through subsequent imaging, a further step of the scanning procedure according to the disclosure is implemented once the first imaging of the microchannel array is performed as shown in Figure 5A.
[0077] This next step of the method according to the disclosure ii-2) requires the displacement, using the XY-positioning stage 130, of the multichannel imaging device 10 relative to the mount 120, over a distance equal of X / N mm in the X direction of the XY- plane. Subsequently, the second (xn=1 , with yn=0) image acquisition sequence ASi in the X-direction of the XY-plane is performed, resulting a second image acquisition of the complete K_x_L array of microchannels 15q yet displaced over a second distance of X / N mm in the X direction.
[0078] The respective images of the various optical channels OCk.i in the K_x_L microchannel array 15qis shown in Figure 5B and can likewise be denoted as a matrix shown below:
[0079] «0100»<<01 01 »<<0102>x<0103>><<0104>>«0105»
[0080] «0110»<<01 11 »<<0112>><<0113>><<0114>><<0115»
[0081] «0120»<<0121 »<<0122>x<0123>x<0124>><<0125» «0130»<<01 31 »<<0132>x<0133>><<0134>>«0135» «0140»<<01 41 »<<0142>><<0143>x<0144>>«0145» «0150»<<01 51 »<<0152>x<0153>><<0154>>«0155»
[0082] Subsequently, step ii-2) of the method according to the disclosure is repeated (index n becomes 2) through the displacement, using the XY-positioning stage 130, of the multichannel imaging device 10 relative to the mount 120, over a third distance (xn=2) equal of X / N mm in the X direction of the XY-plane. Subsequently, the third (xn=2) image acquisition sequence AS2 in the X-direction of the XY-plane is performed, resulting a third image acquisition of the complete K_x_L array of microchannels 15qyet displaced over a third distance of X / N mm in the X direction.
[0083] The respective images of the various optical channels OCk.i in the K_x_L microchannel array acquired at the final N-th image acquisition (xn=5) in the X-direction are denoted as a matrix shown below: <<0500»<<0501 »<<0502>><<0503>><<0504>>«0505» «0510»<<051 1 >><<0512>><<0513>x<0514>>«0515» «0520»<<0521 »<<0522>x<0523>x<0524>><<0525» «0530»<<0531 »<<0532>x<0533>x<0534>><<0535» «0540»<<0541 »<<0542>x<0543>x<0544>><<0545» «0550»<<0551 »<<0552>x<0553>x<0554>><<0555»
[0084] In other words, the image sequences are repeated for a total of N times (n e [0, 1 , 2, ... , N-2, N-1]) and in the particular example of the microchannel array having 6_x_6 optical channels the total image acquisition in the X-direction requires six images, wherein the XY-positioning stage 130 displaces the multichannel imaging device 10 relative to the mount 120 over a total distance (N_x_X / N) of X mm in the X direction of the XY-plane.
[0085] In a similar manner, the above detailed image acquisition is repeated N times in the Y-direction. Thus step ii-2) of the method according to the disclosure is also repeated for each position of the multichannel imaging device 10 at its N discrete X-positions along the X-direction, through the displacement, using the XY-positioning stage 130, relative to the mount 120, over a subsequent distances equal of Y / N mm in the Y direction of the XY- plane.
[0086] For example, Figure 5C shows the microchannel array 15qbeing displaced from the initial orientation of Figure 5A over one distance (yn=1 , with xn=0) of Y / N in the Y direction of the XY-plane. The respective images of the various optical channels OCk.i in the K_x_L microchannel array as shown in Figure 5C can likewise be denoted as a matrix shown below: «1000»<<1 001 »<<1002>x<1003>><<1004>>«1005» «1010»<<101 1 >><<1012>><<1013>><<1014>>« 1015» «1020»<<1 021 »<<1022>x<1023>x<1024>><<1025» «1030»<<1 031 »<<1032>x<1033>><<1034>>«1035» «1040»<<1 041 »<<1042>x<1043>><<1044>>«1045» «1050»<<1 051 »<<1052>><<1053>><<1054>>«1055»
[0087] Likewise, in Figure 5D another image acquisition sequence is depicted, wherein the multichannel imaging device 10 is displaced relative to the mount 120, over two distances X / N mm (xn=2) in the X direction of the XY-plane and one distance Y / N in the Y-direction of the XY-plane (yn=1).
[0088] The corresponding matrix with respective annotations for the images acquired by the various microchannels in the K_x_L array as shown in Figure 5D can likewise be denoted as shown below: <<1200»<<1201 »<<1202>><<1203>><<1204>>«1205» «1210»<<121 1 >><<1212>><<1213>><<1214>>«1215» «1220»<<1 221 »<<1222>><<1223>x<1224>>«1225» «1230»<<1 231 »<<1232>x<1233>x<1234>><<1235» «1240»<<1 241 »<<1242>x<1243>x<1244>><<1245» «1250»<<1 251 »<<1252>x<1253>x<1254>><<1255»
[0089] Likewise, Figure 5E depicts the matrix with respective annotations for the images acquired by the various optical channels OCk.i in the K_x_L microchannel array, in the situation wherein the multichannel imaging device 10 is displaced relative to the mount 120, over N distances X / N mm (nx=N-1 , here xn=5) in the X direction of the XY-plane and N distances Y / N in the Y-direction of the XY-plane (ny=N-1 , here yn=5): «5500»<<5501 »<<5502>x<5503>x<5504>><<5505» «5510»<<551 1 >><<5512>><<5513>x<5514>>«5515» «5520»<<5521 »<<5522>><<5523>><<5524>>«5525» «5530»<<5531 »<<5532>><<5533>><<5534>>«5535» «5540»<<5541 »<<5542>><<5543>><<5544>>«5545» «5550»<<5551 »<<5552>><<5553>><<5554>>«5555»
[0090] With this scanning method as outlined above, the whole sample present in the mount 120 can be imaged without interruptions. By displacing the mount 120 / the multichannel imaging device 10 relative to each other by means of the XY-positioning stage 130 is it possible to capture N2(N times in the X-direction and N times in the Y-direction) captured images in the XY plane. Accordingly, the blind areas between each field of interest of the individual microchannels 15qboth in the X as well as the Y direction of the XY-plane of the mount 120 can be adequately covered and imaged by the whole microchannel array through the incremental displacements in the X as well the Y direction.
[0091] The number of scanning steps N is linearly related to the outer dimension of each individual microchannel and the associated field of view of that microchannel. In case of an outer dimension of X_x_Y mm2and a field of view of X / N_x_Y / N mm2a number of N scans ASnare performed by the multichannel imaging device in both the X-direction and the Y-direction. For each scanning step, the XY-positioning stage 130 displaces the multichannel imaging device 10 relative to the mount 120, over a distance of X / N mm in the X direction of the XY-plane and subsequently over a distance of X / N mm in the Y direction of the XY-plane.
[0092] Each one of the NxN captured images ASncomprises by K_x_L fields of interest (as there are K_x_L microchannels OCk.i which are used NxN times for image acquisition). The K_x_L fields of interest each have a field of view of X / N_x_Y / N mm2and corresponds to a different microchannel OCk,i. As a result, the total fields of interest in the image acquisition are N2x (K_x_L).
[0093] In a further example, the method further comprises the step of iii) storing, using the storage unit 160, each array of images I (yn, xn, k, I) acquired with each step ii-1). Accordingly, the array of images can be used at a later stage in order to compose a complete image of the sample using the data processing unit 150.
[0094] It is noted, that it is preferred to position, prior to step i) or step ii), using the XY-positioning stage, the multichannel imaging device relative to the mount at an initial position, such that the microchannel OCo.o is located at the top left part of the total desired FOV. The top left part of the total desired FOV is positioned in the origin (0,0) as defined by the X and Y axes (in the various Figures 5A-5E) of the XY-plane of the mount 120 on which the sample is deposited for imaging purposes. With this orientation, the OCo.o center is displaced placed X / N units to the right (in the X-direction, seen in the plane of the paper) and Y / N units downward (in the Y-direction, seen in the plane of the paper) from the top left corner of the desired FOV.
[0095] All the segmented images (fields of interest) as acquired with the image acquisition sequences, in total N2x (K_x_L), thus 900 in number in the example presented above, are stored by means of their unique matrix annotation ynxnkl, in accordance with the various matrix annotations depicted above.
[0096] The various segmented images acquired during the incremental, discrete imaging steps in both the X and Y direction and belonging to the same optical channel OCk.i can now be combined or stitched together. This results in a total image of the sample being imaged without any loss of information. The order of the combining or stitching of the various segmented images belonging to the same optical channel OCk.i resembles a matrix.
[0097] In particular, the method according to the disclosure of composing a composite image of a sample using the arrays of images l(yn, xn, k, I) acquired with the image acquisition method according to the disclosure comprises the steps of:
[0098] (a) retrieving, from the storage unit 160 via the signal line 160a using the data processing unit 150, for each optical channel OCki, the arrays of images l(yn, xn, k, I) acquired in the X and Y direction of the XY-plane, and
[0099] (b) combining, using the data processing unit 150, for each optical channel OCki, the respective images in the sequential order of both the X-direction and the Y-direction.
[0100] The order of combining or stitching is shown below and resembles a matrix.
[0101] Using the acquired segmented images of the example presented above, such combined / stitched matrix of five segmented images (in both the X and Y direction, hence in total 25 segmented images) for the first optical channel OCoo is: «0000»<<0100»«0200»«0300»«0400» -> yn=0, xne [0, 1, 2, 3, 4])
[0102] «1000»«1 100»<<1200»«1300»«1400» -> yn=1 , xne [0, 1, 2, 3, 4])
[0103] «2000»<<2100»«2200»«2300»«2400» -> yn=2, xne [0, 1, 2, 3, 4])
[0104] «3000»<<3100»«3200»«3300»«3400» -> yn=3, xne [0, 1, 2, 3, 4])
[0105] «4000»<<4100»«4200»«4300»«4400» -> yn=4, xne [0, 1, 2, 3, 4])
[0106] Similarly, when using the acquired segmented images of the example presented above of each of the optical channels OCki, the combined / stitched matrix of the 25 segmented images of each 36 optical channels OCki, (hence 25x6x6 = 900 unique annotated images l(yn,xn,k,l)) is:
[0107] «0000»<<01 00»... «0400>><<0001 >>«0101 >>... <<0405>>
[0108] «1000»<<1 100»... «1400>><< 1001 »«1101 >>...<< 1405>>
[0109] «4000»<<41 00»... <<4400X<<4001 >>«4101 >>... <<4405>>
[0110] <<0010X<<0110»... <<0410X<<0011»«0111>>...<<4415>>
[0111] «4010»<<41 10»... <<4410X<<4011 >><<4111 >> ... <<4415>>
[0112] «4050»<<41 50»... <<4420X<<4051 >>«4151 >>... <<4455>>
[0113] Accordingly, the whole sample present in the mount can be imaged without interruptions and subsequently a composite image can be composed from the various unique segmented images l(yn,xn,k,l) with the assistance of a multichannel imaging apparatus 100 implementing a multichannel imaging device 10 having reduced constructional dimensions, yet with an improved optical setup in terms of increased FOV, resolution, and magnification. LIST OF REFERENCE NUMERALS USED
[0114] 1 object
[0115] 2 image(or sensor plane)
[0116] 100 multichannel imaging apparatus
[0117] 101 mounting frame
[0118] 102 pedestal
[0119] 103 guiding system or guiding rails
[0120] 110 light source
[0121] 111 light exit face
[0122] 115 support for light source
[0123] 120 mount
[0124] 121 sample holding area
[0125] 130 XY-positioning stage
[0126] 135 support for XY-positioning stage
[0127] 140 composite light sensitive sensor
[0128] 145 support for composite light sensitive sensor
[0129] 150 data processing unit
[0130] 160 storage unit
[0131] 160a signal line
[0132] 10 multichannel imaging device
[0133] 11nfirst microlens element
[0134] 12nmicro-aperture
[0135] 13nsecond microlens
[0136] 15noptical channel
[0137] 15a entrance
[0138] 15b exit
[0139] 15z channel optical axis
[0140] 1100 first microlens array
[0141] 1200 micro aperture array
[0142] 1300 second microlens array
Claims
CLAIMS1. A multichannel imaging device, the device at least comprising: an array of K_x_L optical channels, with k and I being an integer number of 2 or more, with each optical channel having an entrance and an exit for light impinging on the entrance, as well as a channel optical axis, wherein each optical channel is formed as an ommatidium comprising - seen from the entrance in the direction of the exit - a first microlens element at the entrance, a micro aperture, and a second microlens at the exit, as well as wherein, for each optical channel, the first microlens element, the micro aperture, and the second microlens have an optical axis which coincides with the channel optical axis of the associated optical channel.
2. The multichannel imaging device according to claim 1 , further comprising a composite light sensitive sensor for receiving light exiting from each second microlens element and outputting electric signals representing the light being exited by each second microlens element;3. The multichannel imaging device according to claim 1 or 2, the channel optical axes of the array of optical channels extend parallel to each other, such that each optical channel has an unique point of view.
4. The multichannel imaging device according to any one of the preceding claims, wherein the first microlenses are arranged in a first microlens array.
5. The multichannel imaging device according to any one of the preceding claims, wherein the micro apertures are arranged in a micro aperture array.
6. The multichannel imaging device according to any one of the preceding claims, wherein the second microlenses are arranged in a second microlens array.
7. The multichannel imaging device according to any one of the preceding claims, wherein the first microlens elements and / or the second microlens elements have a refractive index of n between 1.4 and 1.6, in particular between 1.49 and 1.50 and in particular n = 1.491756.
8. The multichannel imaging device according to any one of the preceding claims, wherein each microchannel has an outer dimension of X_x_Y mm2and a field of view of X / N_x_Y / N mm2, with n being an integer number of {2, 3, 4, 5, ...}.
9. The multichannel imaging device according to any one of the preceding claims, wherein the first microlens elements and / or the second microlens elements have a rectangular or spherical configuration.
10. A multichannel imaging apparatus comprising: a light source structured to emit electromagnetic radiation in the visible region of the electromagnetic spectrum towards a mount structured to accommodate a sample to be illuminated by the electromagnetic radiation being emitted by the light source; a multichannel imaging device according to any one of the preceding claims and structured to receive electromagnetic radiation being transmitted through the sample accommodated on the mount, as well as an XY-positioning stage for positioning the mount and / or the multichannel imaging device relative to each other in a XY-plane perpendicular to the propagation direction of the electromagnetic radiation through the multichannel imaging device.
11. The multichannel imaging apparatus according to claim 10, further comprising a mounting frame of accommodating the light source, the mount, the multichannel imaging device and the XY-positioning stage.
12. The multichannel imaging apparatus according to claim 10 or 11 , further comprising a data processing unit for receiving and processing the electric signals outputted by the composite light sensitive sensor and generate an array of images representing the sample being illuminated.
13. The multichannel imaging apparatus according to claim 12, further comprising storage means of storing each array of images acquired.
14. A computer implemented method for imaging an sample accommodated in a multichannel imaging apparatus according to any of the claims 10-13 implementing a multichannel imaging device according to any of the claims 1-9 having an array of K_x_L optical channels OCki, with k e [0, 1 , 2, ..., K-1] and I e [0, 1 , 2, ..., L-1], wherein each microchannel OCki has an outer dimension of X_x_Y mm2and a field of view of X / N_x_Y / N mm2, the method comprising the steps of: i) providing a sample in the mount of the multichannel imaging apparatus; ii) performing in both an X-direction and an Y-direction of an XY-plane perpendicular to perpendicular to the propagation direction of the electromagnetic radiation through the multichannel imaging device, using the XY-positioning stage and the multichannel imaging device, a number of n image acquisition sequences ASn, with n e [0, 1 , 2, ..., N-1], with each n image acquisition sequences ASnconsisting of: ii-1) acquiring, using the composite light sensitive sensor, from the sample and from each optical channel OCki of the multichannel imaging device, an array of images l(yn, Xn, k, I);ii-2) displacing, using the XY-positioning stage, the multichannel imaging device relative to the mount, over a distance of X / N (Y / N) mm in the X (Y) direction of the XY- plane.
15. The computer implemented method according to claim 14, further comprising the step of: iii) storing, using the storage unit, each array of images l(yn, xn, k, I) acquired with each step ii-1).
16. The computer implemented method according to claim 14 of 15, further comprising the step of: iv) prior to step i) or step ii), positioning, using the XY-positioning stage, the multichannel imaging device relative to the mount at an initial position, such that the microchannel OCoo is located at the origin (0,0) as defined by the X and Y axes of the XY- plane.
17. A computer implemented method of composing a composite image of a sample using the arrays of images I (yn, xn, k, I) acquired with the method according to any one or more of the claims 14-16 comprising the steps of:(a) retrieving, from the storage unit, for each optical channel OCki, , the arrays of images I (yn, xn, k, I) acquired in the X and Y direction of the XY-plane, and(b) combining, using the data processing unit, for each optical channel OCki, the respective images in the sequential order of both the X-direction and the Y-direction.
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