Automated laser beam control

Abstract

Example embodiments provide a control device and a biomedical illumination device enabling multiwavelength laser line generation with automated beam alignment. The control device may be configured to determine, based on monitored output beam pattern of the biomedical illumination device for illumination of a microscopic sample, a position of one or more beams of the output beam pattern in relation to a target position of the one or more beams within the output beam pattern; determine instructions for one or more actuator-controlled optics of the biomedical illumination device configured for beam steering to change a deflection angle of the actuator-controlled optics based on a difference between the determined position of the one or more beams of the output beam pattern and the target position of the one or more beams within the output beam pattern; and transmit the instructions to the one or more actuator-controlled optics.

Description

[0001] AUTOMATED LASER BEAM CONTROL

[0002] TECHNICAL FIELD

[0003] The present application generally relates to biomedical devices. Some example embodiments of the present application relate to automatic adjustment of laser beam positions for more precise alignment of an output beam pattern of a biomedical device.

[0004] BACKGROUND

[0005] Laser beam alignment is needed in multiple different areas in the field of biomedical applications, such as flow cytometry, DNA sequencing and cell sorting. The alignment is usually done by an operator of a biomedical illumination device. The alignment is performed on-site by manually aligning optical components of the biomedical illumination device. Various biomedical applications, such as the flow cytometry and sequencing applications, may require precise illumination for microfluid components. Hence, it would be beneficial to provide improvements at least for the optical subsystems of biomedical devices.

[0006] SUMMARY

[0007] This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the detailed description. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter.

[0008] Example embodiments enable automated control of actuator- controlled optics for laser beam alignment. Hence, faster and more precise beamalignment may be provided, without a need for manual intervention by an operator. Further example embodiments are provided in the dependent claims, the description, and the drawings.

[0009] According to a first aspect a control device for a biomedical illumination device is provided. The control device may comprise at least one processor; and at least one memory comprising instructions which, when executed by the at least one processor, cause the control device at least to: determine, based on monitored output beam pattern of the biomedical illumination device for illumination of a microscopic sample, a position of one or more beams of the output beam pattern in relation to a target position of the one or more beams within the output beam pattern; determine instructions for one or more actuator-controlled optics of the biomedical illumination device configured for beam steering to change a deflection angle of the actuator-controlled optic based on a difference between the determined position of the one or more beams of the output beam pattern and the target position of the one or more beams within the output beam pattern; and transmit the instructions to the one or more actuator-controlled optics.

[0010] According to an example embodiment of the first aspect, the instructions are determined using a numerical method configured to minimize the difference between the determined position and the target position of the one or more beams.

[0011] According to an example embodiment of the first aspect, the numerical method comprises at least one of the following: a Nelder-Mead method or a Powell’s method.

[0012] According to an example embodiment of the first aspect, the control device is caused to: obtain control variable values for the actuator-controlled optics, wherein the actuator-controlled optics are configured to control the deflection angle based on the control variable values; obtain the target positions of beams in the output beam pattern; receive, from an optical sensor configured to monitor the beams steered by the actuator-controlled optics based on the control variable values, data indicative of the positions of the beams in the output beam pattern; determine the position of the one or more beams based on the data received from the optical sensor; calculate an error based on the determined position and the target position of the one or more beams, wherein the error is indicative of the difference between the determined position of the one or more beams of the output beam pattern and the target position of the one or more beams; compare the calculated error to a tolerance; based on the comparison, update the control variable value for at least one of the actuator-controlled optics until the calculated error is within the tolerance, wherein the update is performed by the numerical method based on the calculated error and associated control variable values; and wherein the transmitted instructions comprise the updated control variable value for at least one of the actuator-controlled optics.

[0013] According to an example embodiment of the first aspect, the control device is further caused to: perform pre-processing of the data indicative of the positions of the beams with at least one of interpolation or curve fitting; and perform the error calculation based on the pre-processed data.

[0014] According to an example embodiment of the first aspect, the control device is further caused to: determine, based on data used for monitoring the output beam pattern, at least one metric indicative of beam quality; compare the at least one metric to an associated threshold for beam quality, wherein the threshold is determined based on historical data obtained from multiple biomedical illumination devices or a static predefined threshold value; based on the comparison, predict if maintenance of one or more components of the biomedical illumination device is needed; and provide a notification to a user for maintenance of the one or more components of the biomedical illumination device based on the prediction.

[0015] According to an example embodiment of the first aspect, the at least metric is indicative of at least one of gaussian beam quality, an amount of diffractions and noise, beam intensity level, beam top-hat quality, or long-term alignment quality.

[0016] According to an example embodiment of the first aspect, the control device is further caused to: determine, based on data used for monitoring the output beam pattern, at least one metric indicative of data quality for beam monitoring; compare the at least one metric to reference data for data quality; and provide a notification to a user about a detected problem with the data quality based on the comparison.

[0017] According to a second aspect, a biomedical illumination device is provided. The biomedical illumination device comprises at least: a plurality of laser light sources configured to provide beams of one or more wavelengths, wherein one or more of the beams are directed towards one or more actuator-controlled optics; and the one or more actuator-controlled optics configured to steer the one or more beams to provide an output beam pattern for illumination of a microscopic sample, wherein at least one actuator-controlled optic is configured for steering a position of the respective beam within the output beam pattern automatically according to instructions received from a control device according to the first aspect.

[0018] According to an example embodiment of the second aspect, the one or more actuator-controlled optics are configured to steer the one or more beams for passing through a beam shaping element; and the biomedical illumination device further comprises the beam shaping element configured to output the beam pattern for illumination of a microscopic sample based on the steered beams.

[0019] According to an example embodiment of the second aspect, the actuator-controlled optics comprise microelectromechanical system, MEMS, mirrors.

[0020] According to an example embodiment of the second aspect, the biomedical illumination device further comprises at least one actuator-controlled optic configured for steering the whole output beam pattern based on instructions received from the control device and positioned to at least one of receive output beams of the beam shaping element or to provide input beams to the beam shaping element.

[0021] According to an example embodiment of the second aspect, the biomedical illumination device further comprises a beam sampler configured to provide a sample of the output beams for illumination of the microscopic sample to the control device for monitoring of the position of the one or more beams of the output beam pattern.

[0022] According to an example embodiment of the second aspect, the biomedical illumination device further comprises at least one of: an optical sensor configured to provide data indicative of relative positions of the sampled output beams within the output beam pattern to the control device; or magnifying optics configured to receive the sampled output beams from the beam sampler and input the magnified output beams to the optical sensor configured to provide data indicative of relative positions of the sampled output beams within the output beam pattern to the control device. According to an example embodiment of the second aspect, the biomedical illumination device further comprises the control device.

[0023] According to a third aspect, a method comprises determining, based on monitored output beam pattern of the biomedical illumination device for illumination of a microscopic sample, a position of one or more beams of the output beam pattern in relation to a target position of the one or more beams within the output beam pattern; determining instructions for one or more actuator-controlled optics of the biomedical illumination device configured for beam steering to change a deflection angle of the actuator-controlled optic based on a difference between the determined position of the one or more beams of the output beam pattern and the target position of the one or more beams within the output beam pattern; and transmitting the instructions to the one or more actuator-controlled optics.

[0024] According to an example embodiment of the third aspect, the instructions are determined using a numerical method configured to minimize the difference between the determined position and the target position of the one or more beams.

[0025] According to an example embodiment of the third aspect, the numerical method comprises at least one of the following: a Nelder-Mead method or a Powell’s method.

[0026] According to an example embodiment of the third aspect, the method comprises obtaining control variable values for the actuator-controlled optics, wherein the actuator-controlled optics are configured to control the deflection angle based on the control variable values; obtain the target positions of beams in the output beam pattern; receiving, from an optical sensor configured to monitor the beams steered by the actuator-controlled optics based on the control variable values, data indicative of the positions of the beams in the output beam pattern; determining the position of the one or more beams based on the data received from the optical sensor; calculating an error based on the determined position and the target position of the one or more beams, wherein the error is indicative of the difference between the determined position of the one or more beams of the output beam pattern and the target position of the one or more beams; comparing the calculated error to a tolerance; based on the comparison, updating the control variable value for at least one of the actuator-controlled optics until the calculated error is within the tolerance, wherein the update is performed by the numerical method based on the calculated error and associated control variable values; and wherein the transmitted instructions comprise the updated control variable value for at least one of the actuator-controlled optics.

[0027] According to an example embodiment of the third aspect, the method comprises performing pre-processing of the data indicative of the positions of the beams with at least one of interpolation or curve fitting; and performing the error calculation based on the pre-processed data.

[0028] According to an example embodiment of the third aspect, the method comprises determining, based on data used for monitoring the output beam pattern, at least one metric indicative of beam quality; comparing the at least one metric to an associated threshold for beam quality, wherein the threshold is determined based on historical data obtained from multiple biomedical illumination devices or a static predefined threshold value; based on the comparison, predicting if maintenance of one or more components of the biomedical illumination device is needed; and providing a notification to a user for maintenance of the one or more components of the biomedical illumination device based on the prediction.

[0029] According to an example embodiment of the third aspect, the at least metric is indicative of at least one of gaussian beam quality, an amount of diffractions and noise, beam intensity level, beam top-hat quality, or long-term alignment quality.

[0030] According to an example embodiment of the third aspect, the method comprises determining, based on data used for monitoring the output beam pattern, at least one metric indicative of data quality for beam monitoring; comparing the at least one metric to reference data for data quality; and providing a notification to a user about a detected problem with the data quality based on the comparison.

[0031] According to a fourth aspect, a method comprises providing, by a plurality of laser light sources, beams of one or more wavelengths, wherein one or more of the beams are directed towards one or more actuator-controlled optics; and steering, by the one or more actuator-controlled optics, the one or more beams to provide an output beam pattern for illumination of a microscopic sample, wherein at least one actuator-controlled optic is configured for steering a position of the respective beam within the output beam pattern automatically according to instructions received from a control device according to the first aspect.

[0032] According to an example embodiment of the fourth aspect, the method comprises steering, by the one or more actuator-controlled optics, the one or more beams for passing through a beam shaping element; and outputting, by the beam shaping element, the beam pattern for illumination of a microscopic sample based on the steered beams.

[0033] According to an example embodiment of the fourth aspect, the actuator-controlled optics comprise microelectromechanical system, MEMS, mirrors.

[0034] According to an example embodiment of the fourth aspect, the method comprises steering, by at least one actuator-controlled optic, the whole output beam pattern based on instructions received from the control device, wherein the at least one actuator-controlled optic is positioned to at least one of receive output beams of the beam shaping element or to provide input beams to the beam shaping element.

[0035] According to an example embodiment of the fourth aspect, the method comprises providing, by a beam sampler, a sample of the output beams for illumination of the microscopic sample to the control device for monitoring of the position of the one or more beams of the output beam pattern.

[0036] According to an example embodiment of the fourth aspect, the method comprises at least one of: providing, by an optical sensor, data indicative of relative positions of the sampled output beams within the output beam pattern to the control device; or inputting, by magnifying optics configured to receive the sampled output beams from the beam sampler, magnified output beams to the optical sensor configured to provide data indicative of relative positions of the sampled output beams within the output beam pattern to the control device.

[0037] According to a fifth aspect, an apparatus is disclosed. The apparatus may comprise means for performing the method according to the third or the fourth aspect, or any example embodiment(s) thereof, as provided in the description and / or the claims. According to a sixth aspect, a computer program, a computer program product, or a (non-transitory) computer-readable medium is disclosed. The computer program, computer program product, or (non-transitory) computer- readable medium may comprise instructions, which when executed by an apparatus, cause the apparatus at least to perform the method according to the third or the fourth aspect, or any example embodiment(s) thereof, as provided in the description and / or the claims.

[0038] Many of the attendant features will be more readily appreciated as they become better understood by reference to the following detailed description considered in connection with the accompanying drawings.

[0039] BRIEF DESCRIPTION OF THE DRAWINGS

[0040] The accompanying drawings, which are included to provide a further understanding of the example embodiments and constitute a part of this specification, illustrate example embodiments and together with the description help to explain the principles of the example embodiments. In the drawings:

[0041] FIG. 1 illustrates an example of a biomedical illumination device according to an example embodiment;

[0042] FIG. 2 illustrates an example of a device for automatic beam steering according to an example embodiment;

[0043] FIG. 3 illustrates an example of an automated beam alignment process according to an example embodiment;

[0044] FIG. 4 illustrates an example of an interpolated vertical profile of a beam;

[0045] FIG. 5 illustrates an example of an interpolated vertical profile of a beam zoomed on a peak of the vertical profile;

[0046] FIG. 6 illustrates an example of a beam middle finding based on Gaussian fitting on beams with optical problems;

[0047] FIG. 7 illustrates an example of Gaussian fittings on beams with noise and diffractions;

[0048] FIG. 8 illustrates an example of intensities of different quality top-hat beams over a horizontal axis; FIG. 9 illustrates an example of a method for automated beam alignment according to an example embodiment;

[0049] FIG. 10 illustrates an example of a method for a biomedical illumination device according to an example embodiment.

[0050] Like references are used to designate like parts in the accompanying drawings.

[0051] DETAILED DESCRIPTION

[0052] Reference will now be made in detail to example embodiments, examples of which are illustrated in the accompanying drawings. The detailed description provided below in connection with the appended drawings is intended as a description of the present examples and is not intended to represent the only forms in which the present examples may be constructed or utilized. The description sets forth the functions of the example and a possible sequence of operations for constructing and operating the example. However, the same or equivalent functions and sequences may be accomplished by different examples.

[0053] An objective is to enable automated control of laser beams. This may be achieved with an automated beam alignment process applied for a biomedical illumination device with actuator-controlled optics and an optical sensor feedback.

[0054] According to an example embodiment, a control device is provided for automatic monitoring and correction of beam alignment of a biomedical illumination device. The control device may be configured to adjust position of one or more components of the biomedical illumination device to adjust resulting position of one or more illumination beams. The monitoring and correction operations can be performed by the control device on a long-time scale. For example, the control device may be configured to perform repeated beam alignment automatically without user intervention. The control device may enable faster and more precise control of beam steering, for example, by using a numerical method configured to minimize an error in the beam alignment. Further, a biomedical illumination device configured to receive instructions from the control device is provided. According to an example embodiment, the control device is further configured to monitor at least one of beam quality or quality of monitored data. Based on monitored metrics related to the at least one of beam quality or monitoring data quality, the control device may be configured to perform predictive maintenance and / or notify an operator about detected problems which may affect operation of the biomedical illumination device and also quality of the automated beam alignment process.

[0055] Temperature changes caused by internal electronics or environment, as well as other environmental conditions, can disturb the alignment of the laser beam in applications that require precision. The process described herein enables to steer beams with high precision in a system that is difficult to parametrize with required precision (e.g., in a biomedical illumination device). The process is applicable to be used in different kinds of devices as the process is independent of the optic configuration and may not utilize parameters of the optical system in the alignment process. Further, the alignment process is automated such that no manual alignment of optical components may be needed. When no human input is needed due to the automatically performed alignment process, a possibility of a human error may be eliminated. Further, downtime may be decreased when there is no need to wait for a trained operator to perform the alignment manually on-site.

[0056] The biomedical illumination device may be applicable for various biomedical applications. The illumination device may provide a precise illumination source for micro fluidic components. The biomedical applications may comprise, for example, flow cytometry, DNA sequencing, and cell sorting. For example, in an example embodiment the biomedical illumination device may provide an improved optical part to be used in a flow cytometer. However, application areas of the biomedical illumination device are not limited to the example biomedical applications, and the illumination device may be used also in other applications which may require precise excitation of a sample with multiple wavelengths.

[0057] Biomedical devices operating in changing environments may require repeated alignment and periodic calibrations. Introduction of automated alignment into such devices may abolish the need of regular manual system re-calibrations. As a result, operational lifespan of the device may be increased, and the risks of internal components damages associated with manual interference into the system may be decreased. Moreover, the biomedical illumination device described herein may enable to abolish a need for external power calibration, since it may be possible to have a power calibration integrated into the device. The integrated power calibration may speed up the time needed to set up the biomedical illumination device running. No physical intervention by an operator may be needed. Modules of the biomedical illumination device may be replaceable such that swapping of the modules at the end of their lifetime can be done easily. In one example, the control device may be further configured to perform predictive maintenance based on data used for the beam alignment. Hence, maintenance of components of at least one of the biomedical illumination device or the control device may be performed timely. In addition, quality of the automated beam alignment may be kept high when any anomalies in behavior of the components affecting analysis of the data used for the beam alignment can be detected and used to provide alerts for users.

[0058] For example, in case of a flow cytometer, a laser beam may be focused on a flow cell through which a focused particle cell is streaming. Due to the versatility of flow cells designs, positioning of laser beams may need to be adjusted in x and y directions of the focusing plane. Further, positioning may be performed in z direction to adjust the focusing plane. Moreover, depending on whether a temporal or spatial laser beam separation is utilized in the particular flow cytometer model, the laser beams either may need to be focused to the same spot or be focused separately on the flow cell.

[0059] Introduction of an automated beam steering for each separate laser line to the cytometry laser platform may offer a possibility to adjust the focus of individual lasers depending on the cytometer requirements. Further, with utilization of actuator-controlled optics configured for automatic beam steering, the beam steering can be done without a need for an operator to access the system and make manual internal adjustments. The actuator-controlled optics may comprise, for example, microelectromechanical systems (MEMS) mirrors. In combination with utilization of beam shaping elements, such as diffractive optical elements (DOEs) or refractive optical elements (ROEs), the biomedical illumination device serves the purpose of being a self-adjustable flow cytometrical laser platform capable of precise flow cell regions excitation. FIG. 1 illustrates an example of a biomedical illumination device 100 according to an example embodiment.

[0060] The biomedical illumination device 100 may comprise one or more light sources 102. A light source may be also referred to as an illumination source. A light source 102 may comprise a laser. The one or more light sources 102 may be configured to provide beams of one or more wavelengths. For example, the biomedical illumination device 100 may comprise a plurality of lasers providing laser beams of one or more color channels. A color channel may refer to a specific range of wavelengths or colors within the electromagnetic spectrum emitted by a light source.

[0061] The biomedical illumination device 100 may comprise one or more actuator-controlled optics 104. The one or more actuator-controlled optics 104 may be configured for each color channel of the light sources 102. The actuator- controlled optics 104 may be used to direct light beams coming from the light sources 102. Each of the actuator-controlled optics 104 may comprise a reflective element, such as a mirror or a lens system, controlled by an actuator. Each of the actuator-controlled optics 104 may be configured to rotate with respect to one or more axis. The actuator may refer to an electronic device configured for producing a controlled motion or action in response to an input signal or command. The actuator-controller optics 104 may be configured to perform beam alignment. Beam alignment may refer to directing the beam toward a series of reflective or partially reflective surfaces, such as mirrors or lenses, so that the beam follows some predetermined path. For example, each of the actuator-controlled optics 104 may be configured to guide the respective beam via one or more optical elements (e.g., beam combiners or beam splitters) to pass through a beam shaping element 108. For example, the actuators may be configured to provide tip-tilt degrees of freedom, thereby controlling an angle and a position of the beam on the beam shaping element 108. Based on control variable values input to the actuator, the actuator may be configured to control a deflection angle associated with the actuator-controlled optics. The deflection angle may refer to a mechanical deflection angle or to an optical deflection angle. The optical deflection angle refers to an angle formed between the incident light and reflected light when a light beam from a light source is directed at a mirror (or other used optics). The optical deflection angle is approximately twice the mechanical deflection angle, which refers to the tilt angle of the mirror. The actuator-controlled optics 104 may be, for example, a MEMS mirror, i.e., an electromagnetic mirror incorporating MEMS technology. A MEMS mirror may be configured to deflect and move a focused beam upon exposure. A MEMS mirror may enable compact design and improved speed for beam steering. A MEMS mirror may provide a wide optical deflection angle, high mirror reflectivity and low power consumption.

[0062] Tip-tilt degrees of freedom may refer to two specific types of motion in the context of optical systems, such as imaging devices. The tip-tilt degrees of freedom may enable achieving precise pointing of a beam. Tip movement may refer to rotation around a horizontal (x-)axis and tilt movement may refer to a rotation around a vertical (y-)axis. In general, an x-axis and a y-axis may refer to two perpendicular axes. The x-axis may refer to a horizontal axis along a reflective surface of the mirror and the y-axis may refer to an orthogonal, vertical axis along the reflective surface. In general, both tip and tilt may refer to tilting, turning or rotating around a specific axis. Tilt may refer to a deviation in the direction a beam of light propagates.

[0063] A light source 102 may be configured to emit a beam towards an actuator-controlled optics 104. In other words, the biomedical illumination device 100 may comprise at least one light source 102 per an actuator-controlled optics 104. In an embodiment, the biomedical illumination device 100 may comprise at least two actuator-controlled mirrors 104 for at least two light sources 102, configured to steer a beam of the respective light source 102. Alternatively, only beams of one or more of the light sources 102 may be configured to be steered by one or more respective actuator-controlled mirrors 104. In one example, at least one actuator-controlled optics 104 may be configured to receive a beam from a light source 102, and the biomedical illumination device 100 may further comprise one or more light sources which beams are not directed towards actuator-controlled optics. That is, the biomedical illumination system 100 may comprise both static beams and beams to be steered by the one or more actuator-controlled optics. The biomedical illumination device 100 may further comprise one or more light sources 102 configured to emit a beam towards one or more optical elements other than the actuator-controlled optics 104. The biomedical illumination device 100 may also comprise one or more actuator-controlled optics 104 configured to receive beams of one or more light sources 102 via one or more optical elements. A beam may be also referred to as a light beam or a laser beam.

[0064] The actuator-controlled optics 104 may be configured to steer the beams according to received instructions towards the beam shaping element 108. An actuator-controlled optics 104 may be also configured to steer beam coming from the beam shaping element 108 according to the received instructions. The received instructions may comprise an indication of a desired position (e.g., the deflection angle) of the actuator-controlled optics 104. The received instructions may comprise, for example, instructions to change an angle of the mirror in one or more rotational axis. In one example, the instructions may comprise control variable values. The control variable values may comprise, for example, voltage values to be applied by the actuators for tilting the respective optics. Each actuator-controlled optics 104 may be configured for a tip-tilt rotation in the xy-plane, e.g., to be rotated, turned or tilted about the x-axis or the y-axis with respect to an attachment point of the actuator-controlled optics 104. The actuator-controlled optics 104 may be positioned such that the beams can be steered towards the beam shaping element. The beams may be steered towards the beam shaping element via the one or more optical elements. The actuator-controlled optics 104 may be further configured to enable changing at least one of an angle or a position of the beams passing through the beam shaping element by rotation of the actuator-controlled optics.

[0065] The biomedical illumination device 100 may comprise the beam shaping element 108. The biomedical illumination device 100 may be configured to comprise one or more beam shaping elements 108. The integration of the beam shaping element(s) into the biomedical illumination device may provide a shaped beam as the output. Thus, a need for additional beam-shaping optical assembly may be eliminated and the system operation becomes feasible for operators without a relevant optical background. No manual alignment of several optical components by a trained operator may be required. Because there is no need for the timeconsuming manual alignment, alignment of the several optical components can be performed by the biomedical illumination device more quickly and may not require regular verification. Further, alignments may be reliably repeated when using the biomedical illumination device with automatic beam alignment instead of using manual alignment.

[0066] The beam shaping element 108 may comprise a diffractive optical element. A diffractive optical element (DOE) may refer to an optical component designed to alter the amplitude or phase of light waves (beams) that pass through it. Light transmitted by a DOE can be reshaped to almost any desired distribution. A DOE may be used to encode the shape of a desired intensity pattern, while maintaining other parameters of the incident light source (e.g., beam size, divergence, polarization). Due to design flexibility of DOEs, DOEs can have optical functions which may not be otherwise achieved or can be achieved with more complicated optical systems. Moreover, compared to e.g. refractive optical elements, DOEs are typically much thinner and lighter, thus enabling more compact design.

[0067] However, the beam shaping element 108 may be also implemented by using a refractive optical element (ROE). Benefits of using a ROE, such as micro lens arrays, comprise the ability to use one ROE with a wider spectrum region compared to a DOE, for example. Hence, the number of used beam shaping elements may be decreased when a wider spectrum region is desired. A ROE may be configured to manipulate or control the direction and behavior of light. A ROE may comprise of materials with different refractive indices configured to cause the light to bend or refract when passing through the materials. A ROE may have for example curved surfaces (either concave or convex) which refract light in specific ways to achieve desired optical effects, such as beam shaping.

[0068] The biomedical illumination device 100 may be capable of generating a wide spectrum of possible beam shapes. The beam shape of the outcome beam(s) may depend on the used beam shaping element (e.g., DOE) 108. By selecting a DOE with appropriate properties, the biomedical illumination device 100 may be configured to generate at least one of one or more lines, such as narrow lines, one or more grid patterns, one or more circular shapes or one or more ring patterns. A line beam shape may be used, for example, in flow cytometrical applications. A grid pattern may be used, for example, in DNA sequencing applications. The biomedical illumination device 100 may be also called a multi-wavelength laser beam pattern generator.

[0069] The biomedical illumination device 100 may further comprise one or more dichroic beam combiners 106. Beams of the light sources 102 may be configured to be steered via the actuator-controlled optics 104 and the one or more dichroic beam combiners 106 to the beam shaping element 108. Each dichroic beam combiner 106 may be positioned between the actuator-controlled optics 104 of a respective light source 102 and the beam shaping element 108. A dichroic beam combiner may refer to an optical component that selectively transmits or reflects different wavelengths or colors of light. A dichroic beam combiner may be configured to combine different spectral regions of light. A dichroic beam combiner may be, for example, a dichroic mirror or a dichroic filter.

[0070] The number and arrangement of components depicted in FIG. 1 is provided as one example, and the number and arrangement of the respective components may be also different, depending on an implementation. The biomedical device 100 may comprise multiple light sources 102, multiple actuator- controlled optics 104 and / or multiple dichroic beam combiners 106. The number of dichroic beam combiners may depend on the number of light sources, such that beams coming from one light source are guided through one or more actuator- controlled optics and / or dichroic beam combiners towards a beam shaping element. The biomedical illumination device 100 may further comprise one or more additional beam combiners for additional wavelengths.

[0071] The combined beams may be configured to be guided from the dichroic beam combiners 106 to the beam shaping element 108. As mentioned, the biomedical illumination device 100 may comprise one or more actuator-controlled optics 104 positioned in the optical path of the beams after the beam shaping element 108, i.e., to an optical path of output beams of the beam shaping element 108. Alternatively, or in addition, one or more actuator-controlled optics 104 may be positioned to an optical path of input beams to the beam shaping element 108. The actuator-controlled optics 104 configured to guide the input / output beams of the beam shaping element 108 may enable to adjust the position of light pattern of the beams as a whole. The actuator of the actuator-controlled optics 104 for the whole beam pattern may be configured to adjust position of the mirror 104 according to received instructions, similar as the actuator-controller mirrors 104 configured for individual steering of the beams and positioned before the beam shaping element 108, i.e., at an optical path of input beams of the beam shaping element 108.

[0072] Hence, depending on the amount and configuration of the actuator- controlled optics, e.g., MEMS mirrors, present in the biomedical illumination system 100, steering of the beams in various degrees of freedom can be achieved. The individual illumination beams, e.g., laser beams, can be steered in both axes (e.g., x- and y-axis with respect to a focusing plane), along with the whole beam pattern, which can include various wavelengths. An optimal actuator-controlled optics configuration may depend on requirements of the application.

[0073] One of the actuator-controlled optics 104 may be configured to guide the beams coming from the beam shaping element (e.g., DOE) 108 to a beam sampler 112. Alternatively, the beam shaping element 108 may be positioned such that the output beams are directed to the beam sampler 112. A beam sampler may refer to an optical element configured to extract a portion of input beam(s) for analysis or measurement without significantly affecting the input beam(s). In other words, the beam sampler may enable to sample or monitor properties of a beam without disrupting a path or intensity of the beam. The biomedical illumination device 100 may comprise the beam sampler 112.

[0074] The biomedical illumination device 100 may comprise, or be coupled to, a control device 110. The control device 110 may be configured to receive data from a detector, such as an optical sensor 118, which is sensitive to positions of the beam(s). In one example, the optical sensor 118 may be an image sensor comprised in a camera. The optical sensor, such as the camera, may be integrated to the device 100. The optical sensor 118 may be configured to sample the entire set of beams (e.g., guided via the actuator-controlled optics and / or dichroic beam combiners from the light sources to the DOE). Based on the sampled beams, the optical sensor 118 may provide data indicative of positions of the beams in relation to each other to the control device 110. The beams to be sampled may be received by the optical sensor 118 from the beam sampler 112. The control device 110 may be configured to measure the resulting position of illumination beams in a plane conjugate to a sample illumination plane based on the data received from the optical sensor. Hence, the control device 110 may be able to obtain accurate information to manipulate source beams according to a targeted light pattern at the sample to be illuminated. The sample may be a microscopic sample. The beam sampler 112 may be configured to provide the sample of the beams to the control device 110. Illumination beams may refer to the beams focused to the sample. Source beams may refer to the beams configured to enter the beam shaping element 108, i.e., the beam shaping element 108 may be configured to reshape the source beams into the illumination beams. The biomedical illumination device 100 may further comprise magnifying optics 116 configured to magnify the beams directed towards the optical sensor 118. The magnifying optics 116 may improve precision of the imaging and subsequent analysis.

[0075] The control device 110 may be configured to determine the instructions for the one or more actuator-controlled optics 104 based on the monitored output beam pattern such that an error between the monitored output beam pattern and a target output beam pattern is minimized. The control device 110 may be configured to use a numerical method for the purpose. The numerical method may be configured to minimize on error calculated based on a difference between monitored beam position(s) and target beam position(s), for example, in relation to other beams in the output beam pattern or in relation to an alignment mark. The control device 110 may be configured to monitor the positions at least at startup of the biomedical illumination device 100 and until the beams are correctly aligned. The control device 110 may be also configured to monitor the position of the output beam pattern continuously or at a predetermined interval. After the actuator has adjusted the position of the respective actuator-controlled optics based on the instructions, the actuator may be configured to keep the adjusted position until new instructions are received.

[0076] In one example, the control device 110 may be configured for aligning the illumination beam(s) according to an alignment mark with respect to a mechanical housing of the illuminator / light source. Alternatively, the illumination beams may be aligned based on an external alignment mark or a signal from a flow cell or one of sensors of a micro fluidic system. This could be, e.g., a simple alignment routine to determine a maximum signal from forward scattering sensor for one of the beams and then align others with respect to the signal, or align all beams to separate sensors, or timely in series if the beams are located on same optical axis.

[0077] In one example, the monitored beams may be aligned based on their positions relative to each other. For example, output beam pattern from the beam shaping element may be monitored to adjust positions of the beams within the output beam pattern. The adjustments may be based on target positions of the beams within the output beam pattern. For example, distance(s) between beams may be monitored and compared against given target distances between the beams in the output beam pattern.

[0078] In one example, the control device 110 may be configured to run an algorithm of machine vision tools. The control device 110 may be configured to provide instructions for beam alignment to the actuators of the actuator-controlled optics 104 based on the detected position of the illumination beams with machine vision and a preset target position of the illumination beams. The control device 110 may be configured to obtain information about current position of the actuator- controlled optics 104 from the actuators and determine instructions for adjusting the current position of the actuator-controlled optics 104 to meet the target position (e.g., to tilt [calculated value] degrees in x- or y-axis). The instructions may be determined by the algorithm. The instructions may comprise, for example, angular displacement parameters for at least one of horizontal steer adjustment or a vertical steer adjustment.

[0079] Alternatively, the control device 110 may be configured to provide information about the monitored positions of the illumination beams (e.g., image data) to the algorithm stored and run on another device configured for analysis. The analysis device may be configured to analyze the current position of the beams with respect to the target position of the beams with the machine vision algorithm and provide instructions for one or more of the actuator-controlled optics 104 for beam steering. The analysis device may be external or internal component of the biomedical illumination device 100. The instructions may be provided to the one or more actuator-controlled optics 104, for example, in a form of a transmitted control signal.

[0080] The biomedical illumination device 100 may further comprise a focusing system 114. The focusing system 114 may depend on application, and may be configured, for example, for flow cytometry application. Alternatively, the biomedical illumination device 100 may be configured to be coupled with the focusing system 114, or with different kinds of focusing systems for illumination of different kinds of samples, for example. A focusing system may be configured to focus the illumination beams to the sample.

[0081] The biomedical illumination device 100 may be configured to enable integrated power calibration. Active beam steering may allow for deflecting the beam for beam shape and power measurement for the calibration by the control device 110 without compromising the output power. For example, the control device 110 may comprise or be coupled to a power sensor configured to perform power measurement based on the sample received by the control device 110. If power calibration was performed from a partially deflected beam, there could be a partial power loss when measured as a few percent sample of the total power delivered to an application. Therefore, any changes in the beam quality could influence the calibrated power and cause varying accuracy.

[0082] The beam pattern formed by the biomedical illumination device may be defined by the design of the DOE integrated into it. While in flow cytometrical applications narrow line laser pattern is widely in use, for DNA sequencing applications a grid pattern can be generated. Depending on the particular application field, the DOE installed in the illumination system may be chosen accordingly. If the pattern requirements change, the DOE may be replaced by an operator with an appropriate one. Further, the operator may update information about the target illumination position / pattem of the beams stored, for example, at the control device 110 such that the actuator-controlled optics 104 are able to align the beams based on the new information.

[0083] Since the distance between beams can be adjusted with the actuator- controlled optics, either separated or overlapping lines can be configured over time. The design of the biomedical illumination device may enable providing a compact solution to changing requirements in an illumination geometry of a sample in instances of modified flow cell designs or altered illumination patterns. The compact solution may be enabled as there is no need to design a completely new optical design upon changed illumination needs but same design with active beam steering can fulfil multiple specifications. Also, directly integrated laser technology combined with micro-optics (e.g., DOE) and MEMS technology may allow building compact modules, as opposed to mechanically adjusted mirrors and / or optical elements. Furthermore, utilization of MEMS mirrors may enable to reduce the effect of optical components drift over time. Automatic beam alignment and reconfiguration may be carried out faster compared to manual work, and even during an operation of the device.

[0084] The biomedical illumination device 100 may have a modular structure. Hence, optical elements in the biomedical illumination device 100 may be configured to be detachable and replaceable. For example, the beam shaping element 108 may be changed when requirements for the beam pattern change. Further, broken mirrors 104 and / or their actuators may be changed when needed.

[0085] FIG. 2 illustrates an example of an apparatus 200 for automatic beam steering in a biomedical illumination device according to an example embodiment. The apparatus 200 may comprise a device such as a control device (e.g., control device 110), a monitoring device, a biomedical illumination device, or a component or a combination of components thereof, or in general any apparatus configured to implement functionality described herein.

[0086] The apparatus 200 may comprise at least one processor 202. The at least one processor 202 may comprise, for example, one or more of various processing devices, such as for example a co-processor, a microprocessor, a controller, a digital signal processor (DSP), a processing circuitry with or without an accompanying DSP, or various other processing devices including integrated circuits such as, for example, an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a microcontroller unit (MCU), a hardware accelerator, a special-purpose computer chip, or the like.

[0087] The apparatus 200 may further comprise at least one memory 204. The memory 204 may be configured to store, for example, computer program code 206 or the like, for example operating system software and application software. In an embodiment, the program code 206 may comprise a machine vision algorithm. The machine vision algorithm may comprise a set of instructions to be carried out by a computing device for interpreting and analyzing visual data, such as images of beams of light. The memory 204 may comprise one or more volatile memory devices, one or more non-volatile memory devices, and / or a combination thereof. For example, the memory may be embodied as magnetic storage devices (such as hard disk drives, magnetic tapes, etc.), optical magnetic storage devices, or semiconductor memories (such as mask ROM, PROM (programmable ROM), EPROM (erasable PROM), flash ROM, RAM (random access memory), etc.).

[0088] The apparatus 200 may further comprise a communication interface 208 configured to enable the apparatus 200 to transmit information to other devices, such as to actuators or user devices. The communication interface 208 may be further configured to enable the apparatus 200 to receive information from other devices, such as from the actuator and / or user devices. For example, the apparatus 200 may be configured to receive one or more target parameters for a light / beam pattern from the user device. The target parameters may comprise a target beam pattern and / or a target position of the target beam pattern at a sample to be illuminated. After evaluating current beam pattem / position produced by a biomedical illumination device with respect to at least one of a focusing plane or the one or more target parameters, the apparatus 200 may be configured to transmit instructions for one or more actuators to change position of optics controlled by the respective actuator to adjust the current beam pattem / position. The evaluations may be configured to be performed continuously such that the current position of beam pattern can be aligned with a target position of the beam pattern and kept in the target position. The communication interface 208 may be further configured to provide instructions for one or more other devices, such as to light sources to adjust their power, or to user devices to notify users about performed adjustments and / or detected changes in performance of the biomedical illumination device.

[0089] The communication interface 208 may be configured to provide at least one wireless radio connection, such as for example a 3 GPP mobile broadband connection (e.g. 3G, 4G, 5G). However, the communication interface 208 may be configured to provide one or more other types of connections, for example a wireless local area network (WLAN) connection such as for example standardized by IEEE 802.11 series or Wi-Fi alliance; a short range wireless network connection such as for example a Bluetooth; a wired connection such as for example a local area network (LAN) connection, a universal serial bus (USB) connection or an optical network connection, or the like; or a wired Internet connection. The communication interface 208 may comprise, or be configured to be coupled to, at least one antenna to transmit and / or receive radio frequency signals. One or more of the various types of connections may be also implemented as separate communication interfaces, which may be coupled or configured to be coupled to a plurality of antennas.

[0090] The apparatus 200 may further comprise, or be configured to be coupled to, a user interface 210 comprising an input device and / or an output device. The input device may take various forms such a keyboard, a touch screen, or one or more embedded control buttons. The output device may comprise, for example, a display. The input device may be configured to receive instructions from a user for calibration of beams. The output device may be configured to provide information on current settings for the calibration, monitored data, performed adjustments on beam steering, and the like. In one example, the apparatus 200 may be configured to receive one or more target parameters via the user interface. The target parameters may comprise, for example, a target output beam pattern, a target position of one or more beams for a desired output beam pattern, one or more thresholds associated to a beam quality, and / or initial control variable values for actuator-controller optics. The user interface may be further configured to provide information to the user, such as notifications of a state of a biomedical device monitored by the apparatus 200. A notification may comprise a confirmation that the output beam pattern is within a tolerance. A notification may comprise an alert about a predicted need for a maintenance of the biomedical illumination device. The notification with the alert can comprise information about a detected deterioration of one or more metrics monitored by the apparatus 200. The notification with the alert may further comprise information about one or more components which may have caused the deterioration. When the apparatus 200 is configured to implement some functionality, some component and / or components of the apparatus 200, such as for example the at least one processor 202 and / or the memory 204, may be configured to implement this functionality. Furthermore, when the at least one processor 202 is configured to implement some functionality, this functionality may be implemented using program code 206 comprised, for example, in the memory 204.

[0091] The functionality described herein may be performed, at least in part, by one or more computer program product components such as software components. According to an embodiment, the apparatus 200 comprises a processor or processor circuitry, such as for example a microcontroller, configured by the program code when executed by the processor to execute the embodiments of the operations and functionality described. Alternatively, or in addition, the functionality described herein can be performed, at least in part, by one or more hardware logic components. For example, and without limitation, illustrative types of hardware logic components that can be used include Field-programmable Gate Arrays (FPGAs), application-specific Integrated Circuits (ASICs), applicationspecific Standard Products (ASSPs), System-on-a-chip systems (SOCs), Complex Programmable Logic Devices (CPLDs), Graphics Processing Units (GPUs).

[0092] The apparatus 200 may comprise means for performing at least one method described herein. In one example, the means comprises the at least one processor 202, the at least one memory 204 including instructions (e.g., comprised in the program code 206) configured to, when executed by the at least one processor 202, cause the apparatus 200 to perform the method.

[0093] The apparatus 200 may comprise for example a computing device. The apparatus 200 may further comprise an imaging system configured to provide information on position of beams to the computing device. In an embodiment, the apparatus 200 may comprise, or be configured to be coupled to, a biomedical illumination device. Although the apparatus 200 is illustrated as a single device it is appreciated that, wherever applicable, functions of the apparatus 200 may be distributed to a plurality of devices.

[0094] The apparatus 200 may comprise, or be configured to be coupled to, at least one optical sensor 118. The optical sensor 118 may comprise, for example, a position sensitive detector, such as a camera. The position sensitive detector may be configured for position detection of light beams. For example, the position sensitive detector may be configured to measure a position of a beam pattern in one or two-dimensions on a sensor surface. Alternatively, the apparatus 200 may be configured to receive information from such optical sensor 118. The received information may comprise data on position of one or more imaged light beams. The position data may comprise information on positions of a plurality of light beams relative to a focusing plane and / or relative to each other. The position data may comprise a pattern of the light beams, comprising positions or locations and other parameters of the light beams in relation to each other. The position data may also comprise information on positions or locations of a plurality of light beams relative to a targeted sample position. Position data may comprise at least one of position of the whole beam pattern with respect to a reference position, positions of individual beams of the beam pattern with respect to at least one of reference positions of the individual beams or with respect to the other beams, or a size of the individual beams or the beam pattern with respect to a set target size. The apparatus 200 may be further configured to store machine vision tools. In addition, or alternatively, the apparatus 200 may be configured to store an algorithm trained to detect deviations between an input image of a beam pattern and a target beam pattern. The algorithm may be based on a numerical method configured to minimize an error between the monitored and target beam positions until the error within tolerance.

[0095] The apparatus 200 may be configured to receive as an input at least one of data indicative of positions of beams of a beam pattern or parameter data of the position, and parameter data of a target position for the beam pattern or individual beams in the beam pattern. The apparatus 200 may be configured to compare the position of the beam pattern (or individual beams) to the target position of the beam pattern (or individual beams) based on the image data and / or the parameter data. Based on the comparison, the apparatus 200 may be configured to calculate instructions for steering one or more actuator-controlled optics configured for beam steering.

[0096] In one example, the apparatus 200 may be configured to obtain position data of the one or more actuator-controlled optics. The position data may be based on control variable values of the actuators. The position of the beam pattern is linked with the position data of the actuator-controlled optics. In one example, the position data of the actuator-controlled optics may comprise, for example, an angle and a tilt direction of the mirror with respect to a reference plane. The apparatus 200 may be configured to determine how much and in what direction one or more of the mirrors needs to be steered (e.g., tilted) to arrive at the target position of the beam pattern. The apparatus 200 may be configured to determine instructions to be transmitted to the actuator-controlled optics based on the comparison, the instructions comprising at least one of adjustment instructions (to alter incline of the actuator-controlled optics based on direction and / or value instructions provided by the apparatus 200) or position instructions comprising target position parameters. The apparatus 200 may store information on which actuator-controlled optics are configured for adjustment of which beam(s) and / or the whole beam pattern. The apparatus 200 may also store information on how different kinds of adjustments of positions of the actuator-controlled optics cause changes in positions of individual beams and / or the in the position of the beam pattern. For example, if the apparatus 200 detects that the whole beam pattern needs to be shifted to the right by a certain distance, the apparatus 200 may know or determine that for such adjustment instructions to tilt certain degrees in a certain direction is needed to be transmitted for a specific actuator-controlled optics. Further, if adjustment of a single beam line in the beam pattern is needed, the apparatus 200 may know for which actuator- controlled optics to send instructions, and determine to which direction and how much the actuator-controlled mirrors need to be instructed to tilt based on a difference between the current and a target position of the beam line and a current position of the actuator-controlled optics.

[0097] In one example, in addition or alternatively, the apparatus 200 may be configured to iterative search for control variable values which provide desired alignment of beams. For example, the apparatus 200 may be configured to determine an error in the beam alignment based on the monitored beam positions and used control variable values, and input the error to the numerical method configured to minimize the error resulting from the used control variable values. The numerical method may output an updated control variable value for at least one of the actuator- controlled optics based on the error and one or more previously used control variable values. The update rounds may be performed until the error within a certain limit.

[0098] The apparatus 200 may be further configured to transmit instructions to other devices or components. For example, the apparatus 200 may be configured to perform power calibration of the light sources based on the monitored beams. In addition, or alternatively, the apparatus 200 may be configured to alert a user, such as an operator of the biomedical illumination device, about detected maintenance needs of the biomedical device based on one or more metrics determined by the apparatus 200 from the monitoring data used for the beam alignment.

[0099] FIG. 3 illustrates an example of an automated beam alignment process according to an example embodiment. The alignment process may be performed by an apparatus, such as the control device 110. In general, the control device may be configured to align a laser beam precisely using any kind of actuated beam steering and optical sensor feedback. The alignment process as described herein is useful in multiple different areas, such as flow cytometry, DNA sequencing and cell sorting. The alignment process may enable precisely control of the laser beam’s alignment in an environment that changes, for example, because of temperature changes.

[0100] At operation 300, the alignment process is started. The alignment process may start, for example, in response to the control device receiving initial control variable values for one or more actuator-controlled optics of a biomedical illumination device. The initial control variables may be received from an operator of the biomedical illumination device via a user interface. Alternatively, the initial control variable values may be pre-set. The control device may be also configured to generate the initial control variable values itself at startup of at least one of the control device or the biomedical illumination device. The control device may be also configured to obtain, from the actuators, their current control variable values.

[0101] At operation 302, the control device may be configured to determine control variable values to be inputted to the actuators. At start, the control device may input the initial values. Alternatively, the control device may determine updated values based on the initial values using a numerical method.

[0102] At operation 304, the actuators receive the control variable values from the control device as an input and act accordingly. For example, the control variables may have any values within a given range. The range may depend on extreme positions of the actuator-controlled optics. For example, based on the input control variable value, the actuator may determine a voltage value to be applied, wherein the position of the actuated optics depends on the applied voltage value.

[0103] At operation 306, the control device may be configured to receive target beam positions. The target beam positions may correspond to a targeted output beam pattern for illumination of a sample. The sample may be, for example, a microscopic sample. In one example, a target position of a beam may be indicated with a distance to adjacent beams in the output beam pattern. The target beam positions may comprise parameters indicative of targeted positions of the beams relative to each other and / or in relation to the sample (or a given reference position) to be illuminated on a focusing plane of the output beam pattern.

[0104] At operation 308, the control device may be configured to receive, from an optical sensor, data indicative of current positions of beams directed by the actuator-controlled optics. The data may comprise, for example, image data of an output beam pattern of the biomedical illumination device. The monitored positions may refer to positions of the beams in relation to each other or in relation to the given reference position. In one example, the optical sensor comprises an imaging sensor. For example, a camera may be configured to take on image of current positions of the beams at least in response to changed control variable values of the actuator-controlled mirrors. The camera may receive an indication from the actuator-controlled mirrors when the control variable values have changed, or the camera may detect when the positions of the beams have changed.

[0105] Based on the data indicative of the current positions of the beams and the target positions of the beams, the control device may be configured to calculate a beam offset of at least one of the beams. The control device may be configured to measure, based on the data received from the optical sensor, a position of at least one beam in relation to one or more other imaged beams. The control device may then compare the measured position to a respective target position of the beam to determine the beam offset. Based on the calculated beam offset, the control device may be configured to determine an error. In one example, the error may correspond to the beam offset. In one example, the error may be calculated based on the beam offset and an exponentiation operation. For example, the error may be calculated as £x, wherein a represents the beam offset and x is a pre-set exponent.

[0106] At operation 310, the control device may be configured to compare the calculated error to a tolerance.

[0107] At operation 312, the control device may be configured to determine, based on the comparison, if the error is within the tolerance. If the error is determined to be within the tolerance, the control device may determine, at operation 314, that the alignment is done.

[0108] If the control device determines, based on the comparison, that the error is not within the tolerance, the alignment process may return to operation 302. At operation 302, the control device may be configured to provide the error as feedback to the numerical method configured to minimize the error. Based on the input error and latest control variable values inputted for the actuators (which resulted the error), the numerical method may be configured to output an updated control variable value for at least one of the actuators. The updated control variable value(s) may be provided to the actuator(s), and the updating process may continue until the numerical method finds optimal control variable value(s) and converges. The updating process may end when the error is within the tolerance.

[0109] The numerical method may comprise, for example, a Nelder-Mead method. The Nelder-mead method refers to a simplex search algorithm for unconstrained optimization without derivatives. The Nelder-Mead method may converge relatively quickly with a small error. The numerical method may also comprise, for example, a Powell’s method. Depending on the setup that controls the mirrors, the numerical method can be run in a way that optimizes all or some of the mirrors at the same time. By controlling one beam at the time, that is, updating control variable values of one actuator at the time, it may be easier for the used numerical method to converge, and the beam steering may be performed faster. The optimal way to run the optimization may depend on the beam steering setup. The described alignment process may be performed without a need for a device-specific configuration. Hence, the alignment process may be utilized on a device without an additional calibration. In one example, the error calculation performed by the control device for the feedback can utilize interpolation of the image pixels. This may produce more precise measurement, as without interpolation, the accuracy is bound to a pixel size of the imaging sensor of the camera. Precision of the error calculation may be also increased by utilizing magnifying optics, such as magnifying optics 116, to magnify the beams to be imaged. The pixel size of a typical computer vision cameras is 2-7 pm. When using a camera with 2 pm pixel size, and having a magnifying lens that provides 4x optical magnification, a computational pixel size of 0,5 pm can be obtained when compared to the actual output. In addition, if an interpolation scale of 5 is used for the image pre-processing, the resulting computational pixel size is 0,1 pm. With this relatively small computational pixel size, it is possible to get to sub-micrometer precision in the alignment process. The used imaging sensor, magnifying optics and interpolation scale may depend on an application, and the used values or properties may vary depending, for example, a configured scale of distance between the beams.

[0110] The effect of interpolation can be seen in FIG. 4 illustrating an example of an interpolated vertical profile of a beam. FIG. 4 shows a graph 400 of the interpolated vertical profile of the beam where the added details (interpolated new data points 404) between the original vertical profile’s datapoints 402 can be seen. FIG. 5 illustrates an example of the interpolated vertical profile of the beam of FIG. 4, wherein the graph 400 is zoomed on a peak of the vertical profile. FIG. 4 and FIG. 5 are produced with interpolation scale of 5, which means that between each original data point 402, 4 new data points 404 are generated. In this case the interpolation is done using cubic interpolation, but any suitable interpolation method could be used.

[0111] Precision of measurements performed for the error calculation can be enhanced by use of curve fitting. The curve fitting technique can be employed by the control device to identify maximum intensities and even the widths of the beams. FIG. 6 illustrates an example of a beam middle finding based on gaussian fitting on beams with optical problems. By fitting gaussian function 600 on the vertical profile of gaussian beam 602, the middle of the beam 604 can be found unambiguously even when there is noise in pixel neighborhood. Furthermore, the application of curve fitting can also mitigate the effects of optical noise and diffractions on the setup.

[0112] FIG. 7 illustrates an example of gaussian fittings on beams with noise and diffractions. FIG. 7 shows vertical profiles 700 of two beams and the gaussian fittings 702 of the two beams. As can be seen from FIG. 7, the impact of the effects of optical noise and diffractions may be effectively removed.

[0113] Usage of an optical sensor on the alignment also allows for collection of various metrics from the beam. The metrics can be indicative of beam quality. In addition, or alternatively, the metrics may be related to data quality, such as quality of image data used for monitoring the beams. In one example, a device may be configured to monitor one or more metrics related to at least one of the beam quality or the data quality based on the received data associated with the monitored beams. The data may comprise the data indicative of positions of the beams within the beam pattern. The data may comprise, for example, image data received from the optical sensor. The monitored metrics may be used to improve operation of at least one of the control device 110 or the biomedical illumination device 100. Both sudden and long-term changes in the beam / imaging quality can be detected based on the monitored data and one or more threshold associated with the various metrics. For example, the collected metrics can indicate possible defects caused by long-term usage. Hence, the metrics can be used to enable predictive maintenance of the biomedical illumination device 100. With predictive maintenance, upcoming malfunctions can be noticed before they disrupt the usage of the device. Deterioration of the beam quality can also affect the precision of the beam alignment. The device configured to monitor the metrics may be, for example, the control device 110.

[0114] In one example, the metrics comprise gaussian beam quality. The gaussian curve fitting on the beam profile can be used to measure the difference between the actual beam profile and the gaussian fitting. This could be used as a metric for long-term predictive maintenance, as the gaussian profile quality can decrease in long-term use.

[0115] For example, the control device 110 can be configured to normalize the beam gaussian profile obtained based on the image data so that the maximum intensity is scaled to value 1. Thereafter, the control device 110 may be configured to create a gaussian curve with variance (one of gaussian function's parameters) equal to a target profile of the beam. The normalized beam profile may be subtracted with the optimal gaussian function (e.g., the created gaussian curve), and the resulted values are stored by the device. The resulted values can be recorded over a long period of time across multiple devices to achieve a baseline metric. The multiple devices may refer to multiple biomedical illumination devices 100, or similar devices configured for illumination of a microscopic sample with a beam pattern. If some device starts producing this metric in a way that deviates from the baseline's variance some percentage, for example 10%, the control device 110 may be configured to detect the deviation and give a warning to a user about the gaussian quality.

[0116] In one example, the metrics can comprise beam intensity. Based on the beam intensity, the control device 110 can be configured to determine if there is a need for calibration or that there are optical problems that occur over long-term use (e.g., months or years). For example, the control device 110 may be configured to record pixel intensity values of an individual beam along with a configured intensity (watts) of the beam (e.g., based on laser intensity values). Based on recorded values from multiple devices, the control device 110 may calculate a baseline for what laser light intensity should equal to at what pixel intensity value. For example, for some wavelength of laser light, the intensity of lOOmW equals to pixel value X with wavelength Y on standardized (same exposure time used across all devices) camera exposure time. If some monitored device is run on the alleged intensity of lOOmW, and the pixel value is e.g. 3% lower or higher than the baseline average, the control device 110 may be configured to give a warning about the intensity value. If the pixel value is above a certain threshold, such as 6%, the control device 110 may determine that the laser is out of calibration and results are not accurate. The control device 110 may then provide a notification to the user about the need for a calibration of the laser. The given percentage values are one example, and may depend on use case.

[0117] In one example, the metrics may be associated to long-term alignment monitoring. The control device 100 may obtain, for example, environmental metrics, such as atmospheric conditions or collisions caused by mishandling of the biomedical illumination device, with atmospheric sensors integrated to the biomedical illumination device. These metrics can be compared to long-term beam alignment data to detect beam drifting caused by the atmospheric conditions or mishandling. The metrics associated with the long-term alignment monitoring may further comprise, for example, beam width and beam height data.

[0118] In one example, the metrics may be associated to long-term optical quality monitoring. Based on the monitored metrics, the control device 110 may detect indications of diffraction problems and in general any optical anomalies.

[0119] In one example, the metrics for data quality may be associated to the image sensor. For example, based on changes in intensity of an image background, the control device 110 may be configured to detect if there is tampering associated with at least one of the control device 110 or the biomedical illumination device 100 when turned on. The control device 110 may be further configured to detect, based on the image data, dead pixels of the image sensor. The reference data may thus comprise, for example, previous image frames such that a change in the image background or dead pixels can be detected. Based on detected tampering, dead pixels, or other anomalies, the control device 110 may be configured to notify the user about possible maintenance needs.

[0120] In one example, the metrics may be associated to beam top-hat quality. FIG. 8 illustrates an example of intensities of different quality top-hat beams over a horizontal axis. In general, a top hat profile may refer to a specific type of laser beam intensity or energy distribution characterized by its distinctive shape with an approximately flat plateau in the center (region of uniform intensity) and steep drop- offs at the edges indicating a rapid decrease in intensity. The metrics can comprise, for example, a parameter indicative of inclination at the edges of the top-hat profile and / or parameters indicative of inclination and an amount of deviations on intensity values of the top-hat profile in the center region. For example, based on the intensity of a first top-hat beam profile 800, there can be seen an unwanted inclination on the top-hat profile with descending intensity values on top. Based on the intensity of a second top-hat beam profile 802, it can be seen that inclination of the ascending and descending sides is not optimal. The intensity of a third top-hat profile 804 shows problems based on an amount of deviations on intensity values at top of the top-hat profile. The control device 110 may be configured to detect the deviations from an optimal top-hat profile based on the monitored metrics. The metrics can be used, for example, to monitor intensity stability of the monitored beams. Based on the metrics, the control device 110 can be configured to detect if the intensity stability starts to drift on a long-term usage.

[0121] Time series over time per metric may show associated trends clearly. The longer time the metrics are collected from deployed devices, the better. Based on the collected metrics, variance or trend of the new data can be obtained when compared to "baseline" data created by healthy devices without maintenance needs. The control device 110 may be configured with one or more metric-specific thresholds as alert limits. For example, a threshold for intensity of a beam may be determined based on the data from healthy devices. Based on monitored metrics associated with the top-hat profiles and gaussian profiles, beam quality score thresholding may be determined. Further, the control device 110 may be configured to trigger beam drifting alerts based on measured beam positions between alignments. The thresholds may be determined, for example, based on input data (e.g., historical data comprising imaged output beam patterns) from the multiple devices recorded over a long time period, such as months or years. The recorded historical data may be stored to a cloud. A threshold may be a baseline metric, e.g., an average value, used for comparison against metrics calculated from the real-time data used for automatic beam alignment for the biomedical illumination device 100 under monitoring. In one example, the threshold(s) may comprise static predefined threshold value(s) for the metric(s). The predictive maintenance operations may be performed, for example, by using trained machine learning models or statistical modeling. The machine learning models may be configured to receive the data recorded from the multiple devices for training and the data used for beam alignment for the monitored biomedical illumination device 100 to make the predictions. The machine learning models may be configured to output a result of comparison of one or more determined thresholds against the currently monitored data. In general, the used algorithm (e.g., machine learning model) is configured to compare the current behavior of the biomedical illumination device with its expected behavior based on the historical data. Any deviation can be an indicator of possible deterioration and trigger the alert. The machine learning models may be updated as more data is obtained from the multiple devices used for reference. The baselines for comparison can be obtained from historical data from healthy devices (no maintenance needs) and / or based on recorded maintenance events such that it can be analyzed when certain changes in data can lead to maintenance in the future. In response to the generated alerts, the control device 110 may be further configured to obtain information from the user how the occurred maintenance need was solved. Based on the received information, the control device 110 may be able to learn to determine and give suggestions for the user how the triggered alert could be solved. Maintenance of the biomedical illumination device 100 may be performed timely, e.g., before a component causing the detected problem gets totally broken and / or before the problem causes substantial issues with operation of the biomedical illumination device 100. Further, accuracy of the automatic beam alignment, as well as operations of the biomedical illumination device 100, may be kept at a high level with the predictive maintenance.

[0122] FIG. 9 illustrates an example of a method 900 for laser beam control. The method may be performed by a control device for a biomedical illumination device, such as the control device 110.

[0123] At 902, the method may comprise determining, based on monitored output beam pattern of the biomedical illumination device for illumination of a microscopic sample, a position of one or more beams of the output beam pattern in relation to a target position of the one or more beams within the output beam pattern.

[0124] At 904, the method may comprise determining instructions for one or more actuator-controlled optics of the biomedical illumination device configured for beam steering to change a deflection angle of the actuator-controlled optic based on a difference between the determined position of the one or more beams of the output beam pattern and the target position of the one or more beams within the output beam pattern. In one example, the instructions may be determined by using a numerical method. The numerical method may be used to iteratively find optimal control variable values for the actuator-controlled mirrors such the difference between the resulting output beam pattern and the target beam pattern is minimized. At 906, the method may comprise transmitting the instructions to one or more actuator-controlled optics.

[0125] FIG. 10 illustrates an example of a method 1000 for biomedical illumination according to an example embodiment. The method may be implemented, for example, with a biomedical illumination device. In one example, the biomedical illumination device may comprise a combination of DOE and automated beam steering by MEMS for multi-wavelength biomedical illumination.

[0126] At 1002, the method may comprise providing, by a plurality of laser light sources, beams of one or more wavelengths, wherein one or more of the beams are directed towards one or more actuator-controlled optics.

[0127] At 1004, the method may comprise steering, by the one or more actuator-controlled optics, the one or more beams to provide an output beam pattern for illumination of a microscopic sample, wherein at least one actuator-controlled optic is configured for steering a position of the respective beam within the output beam pattern automatically according to instructions received from a control device. The control device may be, for example, the control device 110. In one example, the biomedical illumination device may comprise the control device 110.

[0128] The method may further comprise outputting, by the beam shaping element, a beam pattern for illumination of a sample based on the steered beams. The sample may be a microscopic sample, such as a cell. The sample may comprise a flow cell. Flow cells may refer to samples cells designed so that liquid samples can be continuously flowed through the beam path.

[0129] Further features of the methods directly result from the functionalities and parameters of the device as described in the appended claims and throughout the specification and are therefore not repeated here. It is noted that one or more operations of the method may be performed in different order.

[0130] It is obvious to a person skilled in the art that with the advancement of technology, the basic idea of the invention may be implemented in various ways. The invention and its embodiments are thus not limited to the examples described above, instead they may vary within the scope of the claims.

[0131] Further features of the methods directly result from the functionalities and parameters of the device as described in the appended claims and throughout the specification and are therefore not repeated here. It is noted that one or more operations of the method may be performed in different order.

[0132] A device may be configured to perform or cause performance of any aspect of the method(s) described herein. Further, a computer program may comprise instructions for causing, when executed, a device to perform any aspect of the method(s) described herein. Further, a device may comprise means for performing any aspect of the method(s) described herein. According to an example embodiment, the means comprises at least one processor, and memory including program code, the at one memory and the program code configured to, when executed by the at least one processor, cause performance of any aspect of the method(s).

[0133] Any range or device value given herein may be extended or altered without losing the effect sought. Also, any embodiment may be combined with another embodiment unless explicitly disallowed.

[0134] Although the subject matter has been described in language specific to structural features and / or acts, it is to be understood that the subject matter defined in the appended claims is not necessarily limited to the specific features or acts described above. Rather, the specific features and acts described above are disclosed as examples of implementing the claims and other equivalent features and acts are intended to be within the scope of the claims.

[0135] It will be understood that the benefits and advantages described above may relate to one embodiment or may relate to several embodiments. The embodiments are not limited to those that solve any or all of the stated problems or those that have any or all of the stated benefits and advantages. It will further be understood that reference to ‘an’ item may refer to one or more of those items.

[0136] The operations of the methods described herein may be carried out in any suitable order, or simultaneously where appropriate. Additionally, individual blocks may be deleted from any of the methods without departing from the scope of the subject matter described herein. Aspects of any of the embodiments described above may be combined with aspects of any of the other embodiments described to form further embodiments without losing the effect sought. The term 'comprising' is used herein to mean including the method, blocks, or elements identified, but that such blocks or elements do not comprise an exclusive list and a method or apparatus may contain additional blocks or elements.

[0137] The terms ‘automated’, ‘automatically’, ‘automatic’ and variations thereof, as used herein, may refer to any process or operation done without human input when the process or operation is performed. However, a process or operation can be automatic, even though performance of the process or operation uses human input, if the input is received before performance of the process or operation.

[0138] As used in this application, the term ‘circuitry’ may refer to one or more or all of the following: (a) hardware-only circuit implementations (such as implementations in only analog and / or digital circuitry) and (b) combinations of hardware circuits and software, such as (as applicable): (i) a combination of analog and / or digital hardware circuit(s) with software / firmware and (ii) any portions of hardware processor(s) with software (including digital signal processor(s)), software, and memory(ies) that work together to cause an apparatus, such as a mobile phone or server, to perform various functions) and (c) hardware circuit(s) and or processor(s), such as a microprocessor(s) or a portion of a microprocessor(s), that requires software (e.g., firmware) for operation, but the software may not be present when it is not needed for operation. This definition of circuitry applies to all uses of this term in this application, including in any claims.

[0139] As a further example, as used in this application, the term circuitry also covers an implementation of merely a hardware circuit or processor (or multiple processors) or portion of a hardware circuit or processor and its (or their) accompanying software and / or firmware. The term circuitry also covers, for example and if applicable to the particular claim element, a baseband integrated circuit or processor integrated circuit for a mobile device or a similar integrated circuit in server, a cellular network device, or other computing or network device.

[0140] It will be understood that the above description is given by way of example only and that various modifications may be made by those skilled in the art. The above specification, examples and data provide a complete description of the structure and use of exemplary embodiments. Although various embodiments have been described above with a certain degree of particularity, or with reference to one or more individual embodiments, those skilled in the art could make numerous alterations to the disclosed embodiments without departing from scope of this specification.

Claims

CLAIMS1. A control device for a biomedical illumination device, comprising: at least one processor; and at least one memory comprising instructions which, when executed by the at least one processor, cause the control device at least to: obtain control variable values for one or more actuator-controlled optics of the biomedical illumination device configured for beam steering, wherein the actuator-controlled optics are configured to control a deflection angle associated with the actuator-controlled optics based on the control variable values; obtain target positions of beams relative to each other within an output beam pattern of the biomedical illumination device; receive, from an optical sensor configured to monitor the beams steered by the actuator-controlled optics based on the control variable values, data indicative of positions of the beams within the output beam pattern for illumination of a microscopic sample; determine, based on the monitored output beam pattern, the position of one or more beams of the output beam pattern in relation to the positions of the other beams within the output beam pattern based on the data received from the optical sensor; calculate an error in beam alignment based on the determined position and the target position of the one or more beams in relation to each other, wherein the error is indicative of the difference between the determined position of the one or more beams of the output beam pattern and the target position of the one or more beams; compare the calculated error to a tolerance; based on the comparison, update the control variable value for at least one of the actuator-controlled optics until the calculated error is within the tolerance, wherein the update is performed by a numerical method configured to minimize the error in beam alignment based on the calculated error and associated control variable values; determine instructions for the at least one of the actuator-controlled optics to change the deflection angle of the actuator-controlled optic, wherein theinstructions comprise the updated control variable value for the at least one of the actuator-controlled optics; and transmit the instructions to the one or more actuator-controlled optics.

2. The biomedical illumination device of claim 1, wherein the numerical method comprises at least one of the following: a Nelder-Mead method or a Powell’s method.

3. The control device of claim 1 or 2, further caused to: perform pre-processing of the data indicative of the positions of the beams with at least one of interpolation or curve fitting; and perform the error calculation based on the pre-processed data.

4. The control device of any preceding claim, further caused to: determine, based on data used for monitoring the output beam pattern, at least one metric indicative of beam quality; compare the at least one metric to an associated threshold for beam quality, wherein the threshold is determined based on historical data obtained from multiple biomedical illumination devices or a static predefined threshold value; based on the comparison, predict if maintenance of one or more components of the biomedical illumination device is needed; and provide a notification to a user for maintenance of the one or more components of the biomedical illumination device based on the prediction.

5. The control device of claim 4, wherein the at least metric is indicative of at least one of gaussian beam quality, an amount of diffractions and noise, beam intensity level, beam top-hat quality, or long-term alignment quality.

6. The control device of any of preceding claim, further caused to:determine, based on data used for monitoring the output beam pattern, at least one metric indicative of data quality for beam monitoring; compare the at least one metric to reference data for data quality; and provide a notification to a user about a detected problem with the data quality based on the comparison.

7. A biomedical illumination device, comprising at least: the control device of any of claims 1 to 6; a plurality of laser light sources configured to provide beams of one or more wavelengths, wherein one or more of the beams are directed towards one or more actuator-controlled optics; and the one or more actuator-controlled optics configured to steer the one or more beams to provide an output beam pattern for illumination of a microscopic sample, wherein at least one actuator-controlled optic is configured for steering a position of the respective beam within the output beam pattern automatically according to instructions received from the control device.

8. The biomedical illumination device of claim 7, wherein the one or more actuator- controlled optics are configured to steer the one or more beams for passing through a beam shaping element; and the biomedical illumination device comprises the beam shaping element configured to output the beam pattern for illumination of the microscopic sample based on the steered beams.

9. The biomedical illumination device of claim 7 or 8, wherein the actuator-controlled optics comprise microelectromechanical system, MEMS, mirrors.

10. The biomedical illumination device of any of claims 7 to 9, further comprising: at least one actuator-controlled optic configured for steering the whole output beam pattern based on instructions received from the control device and positioned to at least one of receive output beams of the beam shaping element or to provide input beams to the beam shaping element.

11. The biomedical illumination device of any of claims 7 to 10, further comprising a beam sampler configured to provide a sample of the outputbeams for illumination of the microscopic sample to the control device for monitoring of the position of the one or more beams of the output beam pattern.

12. The biomedical illumination device of claim 11, further comprising at least one of: an optical sensor configured to provide data indicative of relative positions of the sampled output beams within the output beam pattern to the control device; or magnifying optics configured to receive the sampled output beams from the beam sampler and input the magnified output beams to the optical sensor configured to provide data indicative of relative positions of the sampled output beams within the output beam pattern to the control device.

13. The biomedical illumination device of any of clams 7 to 12, wherein the biomedical illumination device further comprises the control device.

14. A method, comprising: obtaining, control variable values for one or more actuator-controlled optics of the biomedical illumination device configured for beam steering, wherein the actuator-controlled optics are configured to control a deflection angle associated with the actuator-controlled optics based on the control variable values; obtaining, target positions of beams relative to each other within an output beam pattern of the biomedical illumination device; determining, based on the monitored output beam pattern, the position of one or more beams of the output beam pattern in relation to the positions of the other beams within the output beam pattern based on the data received from the optical sensor; calculating, an error in beam alignment based on the determined position and the target position of the one or more beams in relation to each other, wherein the error is indicative of the difference between the determined position of the one or more beams of the output beam pattern and the target position of the one or more beams within the output beam pattern;comparing the calculated error to a tolerance; based on the comparison, updating the control variable value for at least one of the actuator-controlled optics until the calculated error is within the tolerance, wherein the update is performed by a numerical method configured to minimize the error in beam alignment based on the calculated error and associated control variable values; determining instructions for the at least one of the actuator-controlled optics to change the deflection angle of the actuator-controlled optic, wherein the instructions comprise the updated control variable value for the at least one of the actuator-controlled optics; and transmitting the instructions to the one or more actuator-controlled optics.

15. A method, comprising: providing, by a plurality of laser light sources of a biomedical illumination device, beams of one or more wavelengths, wherein one or more of the beams are directed towards one or more actuator-controlled optics of the biomedical illumination device; steering, by the one or more actuator-controlled optics, the one or more beams to provide an output beam pattern for illumination of a microscopic sample, wherein at least one actuator-controlled optic is configured for steering a position of the respective beam within the output beam pattern automatically according to instructions received from a control device of the biomedical illumination device according to any of claims 1 to 6.

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