Optical measurement system, optical platform therefore and method for aligning an optical platform

Abstract

The invention relates to an optical measurement system for performing measurements on a sample. An XY-stage having a sample holder is mounted in a housing. The sample holder holds samples. For measuring, a cantilever, connected to an optical waveguide, is provided. The cantilever mounted on one side of the XY-stage. Mounted on the opposite side of the XY stage is a camera arranged for imaging the sample. According to the invention, the camera is mounted on an optical platform that is removably fixed in the housing. The invention also provides for an optical platform with camera mount, with a temporary source mount and with optical devices for redirecting a beam from a direction generally perpendicular to the base to a direction generally parallel to the base. The invention also provides for alignment methods for aligning an optical platform for cantilever measurement systems.

Description

OPTICAL MEASUREMENT SYSTEM, OPTICAL PLATFORM THEREFORE AND METHOD FOR ALIGNING AN OPTICAL PLATFORMBACKGROUND OF THE INVENTION1. Field of the Invention

[0001] The invention relates generally to systems and method for a measurement device using a cantilever for measuring a sample. The measurement device can be an optical measurement device. The cantilever is part of a position or force measurement set-up. The position of the cantilever is influenced by the sample. The position or change in position of the cantilever is measured, preferably by an optical position detector, which preferably includes an optical waveguide connecting the cantilever with a detector. In position-sensitive photodetectors, the cantilever on a free end of an optical fiber and receives light through the optical fiber. The displacement of the cantilever at the free end of the optical fiber is measured by recording the reflected light and converting the light-interference into a displacement.

[0002] Part of the optical measurement systems and methods using the cantilever is a camera system for capturing and imaging the sample, preferably while being measured.2. Description of the Related Art

[0003] A cantilever in optical measurement systems and methods is known from US 7,916,306, the content of which is fully incorporated in this application. Samples can be loaded in a sample holder. The sample holder can be placed in an XY stage that allows moving one or more samples to a detection location within the optical measurement system. The cantilever is mounted on a Z stage and brought to the detection location. As the XY stage moves the sample in the XY direction with respect to the cantilever, the cantilever can then measure the height of the sample. A photo-sensor can convert the cantilever movement into a measurement value by implementing an optical interferometric cavity. Other applications, including force measurements, are also possible, for example, by the addition of a fine Z-stage and measuring the deflection of the cantilever with respect to motion of the fine z-stage.

[0004] In optical measurement systems and methods there is a need to acquire camera images of the samples, also during measurements. To that end, a camera is directed at the sample when in the detection location. To capture an image with the camera, photons from the sample are to be acquired with the camera. An optical beam from the sample location to the camera is present.

[0005] The requirements or needs for optical imaging in the optical measurement systems that use a cantilever can change over time, requiring a different set-up of the camera and / or the camera capturing system can require maintenance, e.g. as a result of dust settling on the mirrors. Changes in the camera configuration result in downtime of the optical measurement system. Also, the camera set-up in optical measurement systems with a cantilever can be hard to reach.BRIEF SUMMARY OF THE INVENTION

[0006] The present invention addresses at least one of the problems in optical measurement systems and methods. In an embodiment, an optical measurement system for performing measurements on a sample is provided. The optical measurement system comprises a photo-position sensor that uses a cantilever.

[0007] According to embodiments, the optical measurement system comprises a housing, in which an XY-stage is received. The XY stage can receive a sample holder. The sample holder is configured to hold one or more samples. The samples may be in the form of well plates. The XY stage is mounted in the housing. The XY stage can be moved with respect to the housing. In embodiments, the XY stage is moveable in the XY direction of the housing. As a result, the one or more samples held in the sample holder held by the XY stage can be moved within the housing and with respect to the housing. The samples can be positioned in and out of the detection position, where the cantilever is provided for position sensing.

[0008] In embodiments, a cantilever is mounted on one side of XY stage, preferably above the XY stage, in the housing. In embodiments, the cantilever mounted on one side of the XY- stage in the housing. In embodiments, the cantilever is mounted on a Z stage, allowing to move the cantilever along a detection line, which extends generally perpendicular to the movement of the XY stage. The XY stage can move the sample into the detection line. In embodiments, once the Z-stage is positioned in a predetermined detection position, further movement of the Z-stage is prevented, and sampling commences with respect to that predetermined position using the cantilever. The cantilever is preferably connected to an optical waveguide. Preferably the free end of a fiber has the cantilever and the other end of the fiber has a detector.

[0009] There are numerous different ways of implementing an optical interferometric cavity in an optical measurement assembly in accordance with the invention. In the embodiments, the optical interferometric cavity is a Fabry-Perot cavity. In other embodiments, the optical interferometric cavity may be, for example, a Michelson cavity.

[0010] There are numerous different ways of implementing an optical waveguide in an optical measurement system in accordance with the invention. In the embodiments, the optical waveguide is an optical fiber. In embodiments, the cantilever is positioned at an end of the optical fiber. Preferably the cantilever is incorporated in the end of the optical fiber. In embodiments, a electromagnetic radiation detector is connected to the other end of the optical fiber. In other embodiments, the optical waveguide may be comprised in an integrated photonics system.

[0011] There are numerous different ways of measuring the spectral response of the optical interferometric cavity in an optical measurement assembly in accordance with the invention. In the embodiments, an optical interrogator is used that operates in accordance with a technique as described in WO2017077138A1 , the content of which is fully incorporated in this application. In other embodiments, the spectral response may be measured using a technique different from that described in the aforementioned patent publication.

[0012] In embodiments, images are acquired of the sample in the detection position using a camera. The camera is preferably mounted so that the XY stage is sandwiched between, on theone hand, the position sensitive photodetector comprising the cantilever and, on the other hand, the camera. This allows measurements on one side of the XY stage and capturing pictures from the other side. Preferably the XY stage holds a sample holder in the XY plane, and the cantilever is positioned above the XY stage. The camera preferably captures pictures from the bottom side of the sample holder. Embodiments will provide an objective between camera and detection position. Further optical devices can be used to direct the image of the sample into the camera.

[0013] In embodiments, a light source is provided. The light source can be configured to direct light to the sample through elements of the optical tray and / or by being mounted above the XY stage. The light source can be mounted on the optical platform. In an embodiment, a light source mount is provided on the optical platform. In an embodiment, a light beam from the light source is guided to the detection position by optical devices on the optical platform.

[0014] In accordance with a first aspect of the invention, the camera is mounted on an optical platform that is removably fixed in the housing of the optical measurement system with cantilever. This allows replacing the camera set-up, by moving the optical platform, onto which the camera is mounted, in and out of the housing. This also allows easy access to the further optical device mounted on the optical platform outside of the housing. Outside of the housing, the operator can set-up the camera and / or optical devices. After set-up / configuration of the optical platform, the optical platform with the camera and optical devices mounted thereon, is moved into and fixed in the housing.

[0015] In embodiments, removably fixing the optical platform in the housing comprises any means that allows to secure the platform in the optical measurement system and allows removing the optical platform from the fixed position.

[0016] In embodiments, the fixed position in the housing is a predetermined position. The predetermined position will orient the optical platform with respect to the detection position / detection line. This in turn will set the optical beam path of the camera on the optical platform. The optical platform with camera can calibrated, during an alignment procedure outside of the housing, so that optical beam path connects the detection position to the camera.

[0017] In embodiments, the optical platform comprises a mount for the camera. The mount allows fixing the position of the camera on the platform, preferably on a base of the platform. In embodiments, the mount for the camera is a camera position adjustment mount. The camera position adjustment mount allows adjusting the position of the camera, while mounted on the optical platform. As the optical platform can be easily removed from the housing, configuring the position of the camera using the camera position adjustment mount can be performed outside of the housing by the operator, not hindered by other elements of or in the housing of the optical measurement system. Calibrating or aligning the position of the camera can be performed before fixing the optical platform in the housing. This allows fine-tuning of the position of the camera with respect to the detection position and / or the objective. In embodiments, the camera position adjustment mount comprises a motor for adjusting the camera position. This allows autoadjusting, e.g. based on a feedback-loop that uses images captured by the camera.

[0018] In embodiments, the optical platform comprises one or more optical devices removably mounted on the optical platform. In embodiments, the one or more optical devices comprise one or more mirrors mounted on the optical platform. In further embodiments, the optical devices include at least one folding mirror. With the optical devices, a beam path can be constructed on the optical platform, the beam path directing radiation from the sample to the camera.

[0019] In embodiments, the mirror is mounted to reflect electromagnetic radiation directed generally towards a base of the optical platform to generally parallel to the base of the optical platform. This allows capturing a bottom image of the sample, while the camera is mounted to receive an image in a horizontal direction. This allows reducing the volume or space needed for the camera set-up in the housing of the optical measurement system.

[0020] In embodiments, one or more mirrors are mounted on one or more mirror adjustment mounts. This allows adjusting the position of the mirror. The positions can be adjusted outside of the housing. Mirrors can be easily replaced and / or cleaned outside of the housing. In embodiments, the mirror mount has one or more clips for mounting a mirror. The clips can hold a mirror formed as a mirror plate. The mirror adjustment mount can also have one or more adjustable mirror support pins. The pins can be adjusted to reposition the mirrors. Mirrors can be repositioned during an alignment routine which can be performed outside of the housing, before fixing the optical platform in the housing.

[0021] In embodiments, the mirror adjustment mount comprises a motor for adjusting the mirror position. This allows auto adjustment of the mirrors, e.g. during calibration.

[0022] In embodiments, the optical platform has one or more shrouds. The shrouds at least partially surround the beam path on the optical platform. This prevents noise and / or reduces contamination with dust or sample material of the optical devices. The shrouds are preferably positioned between mirrors of the optical platform and / or positioned between a mirror and the camera mount.

[0023] In embodiments, the optical platform comprises a mount for temporarily mounting an electromagnetic radiation source. The mount for temporarily mounting a source allows one example of aligning the beam path on the optical platform. The mount for temporarily mounting a radiation source can mount the source at a position that corresponds with the detection position, when the platform is fixed in the housing. Thereby the source simulates radiation from the sample. By mounting a temporary source on the mount outside of the housing, the optical platform can be aligned such that the beam path from detection position to the camera is aligned.

[0024] In embodiments, the mount for temporally mounting the electromagnetic radiation source is arranged to mount the electromagnetic radiation source to radiate generally towards, preferably perpendicular to, the optical platform. This allows capturing an image from a bottom side of the sample.

[0025] In embodiments, the housing comprises, in a bottom part, a closeable door for loading and unloading the optical platform into and out of the housing. This allows inserting andremoving the optical platform from a closed off housing. During measurements / in operation, the door of the housing is closed.

[0026] In embodiments, the housing comprises, near a bottom part, at least one guide for the optical platform and / or at least one or more stops or bumpers for the optical platform. The guide / stop / bumper help the operator to mount the optical platform in the housing, preferably on a bottom part thereof, underneath the XY stage. The stops / bumpers allow an insertion direction. The guides provide guidance for an insertion direction.

[0027] In embodiments, the housing further comprises a bottom frame that contains the guide and / or at least one or more stops or bumpers for the optical platform. The guide and / or bumpers allow guiding the optical into a predetermined position in the housing.

[0028] In embodiments, suitable locking screws are used to fix the position of the optical platform with aligned beam path in the housing. The optical platform and the housing can have corresponding cavities for mounting the locking screws in a predetermined position in the housing. By having a predetermined position in the housing, aligning the beam path can be performed before inserting the optical platform in the housing.

[0029] In embodiments, openings are made in the housing to accommodate additional light sources or optical components for alternative imaging methods, such as fluorescence microscopy. Openings may also be made for accommodation of additional cables or operational devices.

[0030] In embodiments, an objective is mounted in the housing in an electromagnetic radiation path between the XY stage and the optical platform.

[0031] In embodiments, the cantilever is mounted on a Z-stage.

[0032] In embodiments, the cantilever is mounted to a fine-motion Z-stage that is mounted to the Z-stage.

[0033] In embodiments, a sample holder is configured to receive one or more culture well plates.

[0034] In embodiments, a light source is configured to provide light from above the cantilever and XY stage, and / or a light source is configured to provide light from beneath the sample through part of the optical platform.

[0035] According to a further aspect an optical platform for an optical measurement system with a cantilever is provided. The optical platform can be positioned within the housing of the optical measurement system with cantilever. The optical platform is removably mountable in the housing of the optical measurement system. In embodiments, the optical platform comprises a base onto which is mounted a first mount for an optical source that directs a beam generally towards the base. A second mount for a camera is also mounted on the base of the optical platform. One or more optical devices, preferably mirrors and / or lenses, for guiding the beam from the mount for the optical source to the mount for the camera, are mounted on the optical platform. The mounts and the one or more optical device are fixed or releasably mounted on the base. In embodiments, at least a part of the beam is guided generally parallel to the base. An optical device is present on the optical platform to redirect the beam from a direction towards thebase to a horizontal direction. The optical platform has one or more alignment units to allow positioning of the optical platform in the housing of the optical measurement system. The optical platforms according to any of the aspects of the invention can be combined with any of the features disclosed herein.

[0036] Preferably the camera mount is arranged to receive the beam in a horizonal direction. This results in an optical platform that can be aligned for receiving / guiding a beam and redirecting the beam to a perpendicular direction. This allows to obtain an optical platform that receives radiation / a beam in a direction generally directed at the base, but guides the radiation / beam in perpendicular direction. This allows, e.g. in a housing for an optical measurement system with a cantilever and an XY stage, to position the aligned optical platform under the XY stage, capturing an image of the bottom of the samples, while optical devices including mirrors guide the radiation towards the camera on the optical platform in a horizontal direction. In such housings, the available height is limited, whereas the already present width of the XY stage provides for a lot of available space in the horizontal direction. An optical platform according to this aspect, makes use of the available horizontal space.

[0037] According to a further aspect, an optical platform for an optical measurement system with a cantilever is provided. The optical platform can be positioned within the housing of the optical measurement system with cantilever. The optical platform is removably mountable in the housing of the optical measurement system. The optical platform comprises a base onto which a camera is mounted with a mount for the camera. One or more optical devices for guiding electromagnetic radiation to the camera are mounted on the base of the optical platform. In embodiments, the mount for the camera is a camera position adjustment mount. This allows adjusting the position of the camera during alignment or calibration to increase the optical behaviour of the camera. The position adjustment mount provides further flexibility in mounting a camera on the optical platform and, in use, mounting the camera in the housing of the optical measurement system.

[0038] In embodiments, the optical platform of the further aspects has a positioning system, preferably a locking system, for positioning the optical platform, preferably positioning the base, in a predetermined position within the housing, preferably onto a bottom frame, of the optical measurement system with the cantilever. In embodiments, removably fixing the optical platform in the housing comprises any means that allows to secure the platform in the optical measurement system and allows removing the optical platform from the fixed position. In embodiments, the fixed position in the housing is a predetermined position. The predetermined position will orient the optical platform with respect to the detection position / detection line within the optical measurement system. This in turn will set-up the optical beam path of the camera on the optical platform. The optical platform with camera can calibrated, during an alignment procedure outside of the housing, so that optical beam path connects the detection position to the camera. The optical platform has one or more alignment units to allow positioning of the optical platform in the housing of the optical measurement system. The optical platforms according to any of the aspects of the invention can be combined with any of the features disclosed herein. Inembodiments, the optical platform of the further aspects has at least one folding mirror, wherein preferably at least one mirror is arranged to reflect electromagnetic radiation generally directed at the base to be generally directed parallel to the base.

[0039] In embodiments, the optical platform of the further aspects has a dichroic mirror that is mounted on the base of the platform. This allows capturing images using the principles of fluorescent microscopy. By providing the dichroic mirror on the optical platform, the extra function can be mounted as an extra function or can be removed easily.

[0040] In embodiments, the optical platform of the further aspects has one or more optical devices that comprise one or more mirrors, wherein at least one mirror is mounted on mirror adjustment mounts, preferably held by one or more clips and more preferably supported by one or more adjustable pins.

[0041] An alternative aspect of the invention provides a kit of parts for an optical platform according to any of the embodiments disclosed herein. The kit comprises at least a base for an optical platform, a camera mount and one or more optical devices. The kit can comprise any of the features of the optical platforms according to the further aspects, thereby providing replacement parts for the optical devices on the optical platform that is removably mounted in the housing of the optical measurement system. The kit can be used in any of the alignment methods disclosed herein and can comprise any of the features of the optical platform used for alignment. The kit can comprise any of the features of the optical platform used in any of the optical measurement systems disclosed herein,

[0042] According to yet a further aspect, a method for aligning a beam path of an optical platform is provided. The optical platform is for viewing samples held by an XY-stage in an optical measurement system that has a cantilever.

[0043] In embodiments, the method comprises simulating a beam path of the optical platform. The optical platform will hold optical devices and / or a camera. A beam will be guided over the optical platform. By simulating, e.g. providing a temporary light source such as a laser, the beam path of the optical platform, optical devices and / or cameras mounted or to be mounted on the optical platform can be adjusted to adjust the beam path.

[0044] In embodiments, the method comprises aligning the beam path of the optical platform using the simulated beam path. Using a temporary laser is a known method for simulating a beam path. Aligning comprises any adjustments of the optical devices or camera on the optical platform that results in preparing the optical platform for receiving a beam at a certain entry point and guiding that beam towards a detector or camera on the optical platform.

[0045] According to the invention, the aligning takes place before positioning the optical platform with aligned beam path in the optical measurement system. This allows aligning to be set-up outside of the housing of limited volume of the optical measurement system. This also allows quick replacement of optical platforms with different set-ups.

[0046] In embodiments, simulating a beam path comprises mounting a laser on an optical platform. The laser is removed before positioning the aligned optical platform in the optical measurement system. In embodiments, the laser is mounted in a bracket mounted on the opticalplatform. The bracket can temporarily hold the laser for aligning purposes. The bracket can be removed before inserting the optical platform into the housing.

[0047] In embodiments, the method comprises mounting one or more mirrors on the optical platform in the beam path and wherein aligning comprises adjusting the one or more mirrors mounted on the optical platform. Adjusting mirrors for aligning a beam path is a known technique.

[0048] In embodiments, positioning the optical platform with an aligned beam path in the optical measurement system can comprise opening and closing a door of a housing of the optical measurement system, and / or aligning a position of the optical platform in the optical measurement system by providing alignment bumpers in the housing of the optical measurement system, and / or fixing the aligned optical platform to a bottom in a housing of the optical measurement system. The door of the housing protects the mounted optical platform in the housing. Stops / guides / bumpers can help the operator during inserting and subsequently mounting the optical platform in the housing.

[0049] Preferably the optical platform is mounted to a bottom of the housing, underneath the bottom of samples held in the sample holder that is held in the XY stage. On the other side of the XY stage is the cantilever position sensor.

[0050] In embodiments of the method, aligning comprises aligning a mount that can hold a camera. The mount can be repositioned with respect to a base of the optical platform. In embodiments of the method, aligning comprises providing an auxiliary alignment tool, such as a frosted plate having a hole, and mounting the auxiliary alignment tool in the mount that can hold the camera. The auxiliary alignment tool can be used as an aid during simulation of the beam path to speed up the alignment.

[0051] In embodiments of the method, the method comprises positioning a camera on the optical platform before positioning the optical platform with aligned beam path in the optical measurement system. The camera positioned in the aligned beam path allows capturing images of the samples in the optical measurement system.

[0052] In embodiments of the method, the method comprises providing the camera in a mount on the optical platform and wherein aligning comprises aligning the camera, wherein more preferably aligning comprises adjusting a position of the camera on the optical platform.

[0053] In embodiments of the method, the method preferably comprises positioning one or more shrouds on the optical platform to surround at least partially the aligned beam path.BRIEF DESCRIPTION OF THE DRAWINGS

[0054] The features and advantages of the invention will be appreciated upon reference to the following drawings, in which:FIG. 1 is a view of one embodiment of the optical measurement system.FIG. 2 is an explodes view of the optical system including the optical platform according to a first embodiment.FIG. 3 is a detailed view of the optical platform of FIG. 2. andFIG. 4 is a view of a bracket that can be used with the optical platform of FIG.3.DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

[0055] The following is a description of certain embodiments of the invention, given by way of example only and with reference to the drawings. Referring to FIG. 1 , an optical measurement system 100 is shown. A housing 101 is provided. Housing 101 has a door 102, which can be opened and closed. The door 102 provides, and closes off, access to a bottom part of that housing. FIG. 1 is a schematic representation of the PAVONE products manufactured by the Applicant Optics 11 Life.

[0056] FIG.2 schematically shows elements received within the housing 101. Underneath removable cover 104, frame 220 is mounted and support a Z-stage 221 that carries the cantilever for sample detection.

[0057] The cantilever (not shown) can be connected to an optical waveguide such as a free end of an optical fiber. The end of the optical waveguide and a surface part of the measurement cantilever that faces the end of the optical waveguide form an interferometric cavity. In this embodiment, the interferometric cavity is a Fabry Perot cavity.

[0058] The measurement cantilever may have a length in the order of millimeters and a width in the order of hundreds of microns. For example, the length of the measurement cantilever may be in a range between 0.5 and 5 mm; the width of the measurement cantilever may be in a range between 0.1 and 1 mm. The measurement cantilever may have a thickness in the order of micrometers to hundreds of micrometers. For example, the thickness of the measurement cantilever may be in a range between 1 pm and 100 pm.

[0059] The optical waveguide may be in the form of, for example, a single-mode fiber optic cable that has been cleaved and aligned with the measurement cantilever. The end of the optical fiber may be positioned with respect to the interferometric surface part of the measurement cantilever at a distance comprised in a range between, for example, 0.1 mm and 3 mm.

[0060] The interferometric cavity has a spectral response that depends on an optical path length within the interferometric cavity. The optical path length is defined by two factors. One factor is a distance between the end of the optical waveguide and the interferometric surface part of the measurement cantilever. This distance will be referred to hereinafter as the interferometric cavity length for the sake of convenience. The other factor that defines the optical path length is a refractive index of a medium that exists between the aforementioned two entities that form the interferometric cavity 108. The latter factor may be regarded as constant.

[0061] Measuring the spectral response allows measuring the position of the cantilever with relatively great precision. Measuring a change of the spectral response can be used to measure a force. In case the measurement cantilever flexes, the optical path length within the interferometric cavity changes and, consequently, the spectral response changes. A change in the interferometric cavity length can be quantitively determined with relatively great precision on the basis of a change in the spectral response that is measured. The position of the sample can be calculated on the basis of the change in the interferometric cavity length and several known factors that concern the measurement cantilever. These known factors include the degree of elasticity of the measurement cantilever and a geometric relationship of the sample.

[0062] The Z-stage 221 of the optical measurement system 100 holds the cantilever in a position and can move it to a detection position. The Z-stage is positioned on the detection line for measuring. In this embodiment, the optical measurement system further comprises a sample holder with multiple samples. The sample holder can comprise one or more culture well plates. The sample holder may be positioned in the XY stage 230. The XY stage can move a sample into the detection position for measuring with the cantilever. As illustrated by FIG.2 the samples are held underneath the Z-stage 221 and thereby underneath the cantilever. During measurement sequences, the XY stage can move with respect to the Z-stage and therefore the cantilever.

[0063] Under the XY stage 230, the housing 101 has a bottom frame 240, which mounts the objective 241 . Objective 241 is arranged to collect a beam from the sample held at the detection position. While the cantilever samples from a top side, images of the sample can be captured from the bottom side.

[0064] Light can be directed through the sample in the XY stage 230 by means of a light source 210 mounted to the frame 220 to direct the beam through the sample and to the objective 241 . The light may be an array of light emitting diodes. Light sources can also be directed to the sample through the housing via openings in the housing 101 .

[0065] Images are captured using a camera mounted on an optical platform 250 that is releasably fixed to the bottom frame 240. Door 102 can be opened to access the volume underneath the XY stage 230. The door 102 is opened to position or remove the optical platform 250 in or from the volume underneath the XY stage. During operation / measuring, the door is closed.

[0066] To position the optical platform in a predetermined position in the housing, and thereby in a predetermined orientation with respect to the Z-stage and the detection line, bumpers or guides 244 are provided on the bottom frame. Other guides and bumpers can be used.

[0067] FIG.3 shows a detailed view of the optical platform 300 having a base 301 . The base is formed by a plate. Guiding grooves 303,304 can be aligned with stops or guides on the bottom frame 240. Holes 305,306 allow a fixing screw to releasably fix the optical platform in a predetermined position on the bottom frame. The predetermined position is such that the camera 346 of optical platform 300 will have a beam path directed at the detection position, where the sample is held. Guiding grooves 303,304 and holes 305,306 are examples of aligning units for positioning the optical platform 300 in the optical measurement system with cantilever. The optical platform 300 and the bottom frame 240 of the optical measurement system 100 share a positioning system, preferably a locking system, for positioning / locking the optical platform 300 in a predetermined position in the housing of the optical measurement system 100. That way, the optics on the optical platform 300 can be calibrated outside of the housing of the optical measurement system 100 for use in that calibrated set-up in the optical measurement system 100. The positioning / locking system can be released, allowing removal of the optical platform with optics from the housing, e.g. for cleaning, recalibration and subsequently repositioning in the housing.

[0068] As the optical platform 300 is positioned underneath the XY stage 230 and under the objective 241 , the beam path arrives at the optical platform in a vertical direction, directed towards the base 301 . A first mirror 311 mounted on mirror adjustment mount 310 redirects the beam from a vertical direction to a horizontal direction, generally parallel to the base 301 .

[0069] Mirror 311 is held by four clips 312 on a mount 310 that has position adjustment pins 313 can be adjusted by a user for adjusting the position / angle of the mirror. This causes a change in the beam path.

[0070] In the shown embodiment, an alternative light source can be mounted onto a mount 321 , to direct the beam path to the dichroic mirror 320, which partially directs the beam to the sample, which can fluoresce and direct light back to the camera 346.

[0071] Part of the beam travels to mirror mount 330, which similarly holds a mirror. Mirror mount 330 directs the beam path towards camera 346, which is mounted on camera adjustment mount 340, which is bolted 341 to the base 301 A dial plate 345 allows adjusting the position of the removably mountable camera 346.

[0072] To align the beam path as described above, a bracket 401 according to FIG.4 can be mounted temporarily onto the base 301 of the optical platform 300. Base 301 can have corresponding connection points for mounting screws to fix the bracket 401 at a predetermined location onto the base 301 . The predetermined location is such that the mounting ring 410 of the bracket is positioned to correspond with the objective 241 or positioned on the detection line of the Z-stage, that is in line with the detection position for measuring samples. By temporarily mounting a source such as a laser into mounting ring 410, that laser can be used to simulate the beam path of radiation from the objective 241 / from the sample.

[0073] The mounting ring 410 is positioned such that the simulated beam path is directed towards the base 301 . The bracket allows positioning the mounting ring up or over the mirror mount 310. The beam path will be reflected by mirror 311 to a generally horizontal direction, towards mirror 330 and detector 346.

[0074] In an embodiment, aligning comprises simulating the beam path by mounting a laser in mounting ring 410 in bracket 401 , which is temporary mounted on optical platform 300. By adjusting the positions of the mirrors 311 and 330, light can be directed towards mount 340. In an embodiment, before mounting the camera 346, a frosted plate with a hole or a different auxiliary alignment tool can be used to generally align the beam. Then the frosted plate is replaced by the camera and position of the camera in the mount 340 can be tweaked using dial plate 345.

[0075] Bracket 401 can be removed after aligning. The optical platform with aligned beam path can subsequently be mounted in the housing 101.

[0076] Other beam path simulating methods can be used to align the beam path accordingly.

[0077] Thus, the invention has been described by reference to certain embodiments discussed above. It will be recognized that these embodiments are susceptible to various modifications and alternative forms well known to those of skill in the art. The embodimentsdescribed hereinbefore with reference to the drawings are presented by way of illustration. The invention may be implemented in numerous different ways.

[0078] The invention may be applied in numerous types of products or methods related to optically measuring a functional property of a sample, such as a tissue or a biomaterial. In embodiments, contractile forces are measured. In other embodiments, a stiffness of the sample, e.g. a tissue, may be measured.

[0079] The remarks made hereinbefore demonstrate that the embodiments described with reference to the drawings illustrate the invention, rather than limit the invention. The invention can be implemented in numerous alternative ways that are within the scope of the appended claims. All changes that come within the meaning and range of equivalency of the claims are to be embraced within their scope. Any reference sign in a claim should not be construed as limiting the claim. The verb “comprise” in a claim does not exclude the presence of other elements or other steps than those listed in the claim. The same applies to similar verbs such as “include” and “contain”. The mention of an element in singular in a claim pertaining to a product, does not exclude that the product may comprise a plurality of such elements. Likewise, the mention of a step in singular in a claim pertaining to a method does not exclude that the method may comprise a plurality of such steps. The mere fact that respective dependent claims define respective additional features, does not exclude combinations of additional features other than those reflected in the claims.

[0080] Further modifications in addition to those described above may be made to the structures and techniques described herein without departing from the spirit and scope of the invention. Accordingly, although specific embodiments have been described, these are examples only and are not limiting upon the scope of the invention.

[0081] The following numbered clauses provide embodiments of the invention. Each of the clauses and each of the features in the clauses can be combined with any of the clauses and features mentioned in the clauses, as well as with any of the features disclosed herein, especially in combination with any of the features disclosed in relation to the figures.[Clause 1 .] Optical measurement device for performing measurements on a sample, comprising: a housing; an XY-stage having a sample holder, mounted in the housing, wherein the sample holder is configured to hold the sample; a cantilever, connected to an optical waveguide, the cantilever mounted on one side of the XY-stage in the housing; and a camera, mounted opposite the one side of the XY-stage in the housing, the camera arranged for imaging the sample, wherein the camera is mounted on an optical platform that is removably fixed in the housing. [Clause 2.] Optical measurement system according to any embodiment disclosed in this application or according to any of the claims or clauses or according to clause 1 , wherein the optical waveguide comprises an optical fiber, wherein the cantilever is positioned at an end of the optical fiber,wherein preferably the cantilever is incorporated in the end of the optical fiber and / or an electromagnetic radiation detector is connected to the other end of the optical fiber.[Clause 3.] Optical measurement system according to any embodiment disclosed in this application or according to any of the claims or clauses or according to any of the previous clauses, wherein the optical platform comprises a mount for the camera, wherein preferably the mount for the camera is a camera position adjustment mount for adjusting the camera position, wherein more preferably the camera position adjustment mount comprises a motor for adjusting the camera position.[Clause 4.] Optical measurement system according to any embodiment disclosed in this application or according to any of the claims or clauses or according to any of the previous clause, wherein the optical platform comprises one or more optical devices removably mounted on the optical platform wherein preferably the one or more optical devices comprise one or more mirrors mounted on the optical platform, preferably comprising at least one folding mirror, wherein preferably the folding mirror is mounted to reflect electromagnetic radiation directed generally towards the optical platform to generally parallel on the optical platform, wherein preferably the one or more mirrors are mounted on one or more mirror adjustment mounts, wherein preferably the mirror adjustment mount has one or more clips for mounting a mirror and / or has one or more adjustable mirror support pins, wherein more preferably the mirror adjustment mount comprises a motor for adjusting the mirror position, wherein the optical platform has one or more shrouds, preferably positioned between mirrors of the optical platform and / or positioned between a mirror and the camera mount.[Clause 5.] Optical measurement system according to any embodiment disclosed in this application or according to any of the claims or clauses or according to clause 3 or 4, wherein the optical platform comprises a mount for temporarily mounting an electromagnetic radiation source, wherein preferably the mount for temporally mounting the electromagnetic radiation source is arranged to mount the electromagnetic radiation source to radiate generally towards, preferably perpendicular to, the optical platform.[Clause 6.] Optical measurement system according to any embodiment disclosed in this application or according to any of the claims or clauses or according to any of the previous clauses, wherein the housing comprises, in a bottom part, a closeable door for loading and unloading the optical platform into and out of the housing; and / or the housing comprises, near a bottom part, at least one guide for the optical platform and at least one or more stops for the optical platform; and / or the housing comprises one or more openings for additional / other light sources; and / or the housing comprises one or more openings occupied by cables needed for the functioning of the camera.[Clause 7.] Optical measurement system according to any embodiment disclosed in this application or according to any of the claims or clauses or according to any of the previous clauses, wherein an objective is mounted in the housing in an electromagnetic radiation path between the XY stage and the optical platform; and / or the cantilever is mounted on a Z-stage; and / or the cantilever is mounted on a fine-motion Z-stage attached to a coarse Z-stage; and / or the sample holder is configured to receive one or more well plates. a light source is configured to provide light from the cantilever side, a light source is configured to provide light from the optical platform side.[Clause 8.] Optical platform for, preferably being releasably positionable within a housing of, an optical measurement system with a cantilever, wherein the optical platform comprises: a base, a mount for an optical source that directs a beam generally towards the base, a mount for a camera, and one or more optical devices, preferably mirrors and / or lenses, for guiding the beam from the mount for the optical source to the mount for the camera, wherein at least a part of the beam is guided generally parallel to the base.[Clause 9.] Optical platform for, preferably being releasably positionable within a housing of, an optical measurement system with a cantilever, wherein the optical platform comprises: a base, a camera held by a mount for a camera, the mount for the camera connected to the base, and one or more optical devices for guiding electromagnetic radiation to the camera, wherein the mount for the camera is a camera position adjustment mount.[Clause 10.] Optical platform according to any embodiment disclosed in this application or according to any of the claims or clauses or according to clause 8, wherein further comprising a mount for a camera that holds a camera, wherein the mount for the camera connected to the base, and one or more optical devices for guiding electromagnetic radiation to the camera, wherein the mount for the camera is a camera position adjustment mount,OR optical platform according to any embodiment disclosed in this application or according to any of the claims or clauses or according to clause 9, further comprising a mount for an optical source that directs a beam generally towards the base, a mount for a camera, and one or more optical devices, preferably mirrors and / or lenses, for guiding the beam from the mount for the optical source to the mount for the camera, wherein at least a part of the beam is guided generally parallel to the base.[Clause 11 .] Optical platform according to any embodiment disclosed in this application or according to any of the claims or clauses or according to any of the clauses 8-10, wherein the optical platform has a positioning system, preferably a locking system, for positioning the opticalplatform, preferably positioning the base, in a predetermined position within the housing, preferably onto a bottom frame, of the optical measurement system with the cantilever.[Clause 12.] Optical platform according to any embodiment disclosed in this application or according to any of the claims or clauses or according to any of the clauses 8-11 , wherein at least one of the optical devices is a folding mirror, wherein preferably at least one mirror is arranged to reflect electromagnetic radiation generally directed at the base into generally directed parallel to the base, a dichroic mirror is mounted on the base of the platform, the one or more optical devices comprise one or more mirrors, wherein at least one mirror is mounted on mirror adjustment mounts, preferably held by one or more clips and more preferably supported by one or more adjustable pins.[Clause 13.] Method for aligning a beam path of an optical platform for viewing samples held by an XY-stage in an optical measurement system that has a cantilever, wherein the method comprises: simulating a beam path of the optical platform; aligning the beam path of the optical platform using the simulated beam path, and positioning the optical platform with aligned beam path in the optical measurement system. [Clause 14.] Method according to any embodiment disclosed in this application or according to any of the claims or clauses or according to clause 13, wherein: simulating a beam path comprises mounting a laser on an optical platform, and removing the laser is removed before position the optical platform in the optical measurement system, wherein preferably the laser is mounted in a bracket mounted on the optical platform, and / or the method comprises mounting one or more mirrors on the optical platform in the beam path and wherein aligning comprises adjusting the one or more mirrors mounted on the optical platform, and / or positioning the optical platform with aligned beam path in the optical measurement system comprises: o opening and closing a door of a housing of the optical measurement system, and / or o aligning a position of the optical platform in the optical measurement system by providing alignment bumpers in the housing of the optical measurement system, and / or o fixing the aligned optical platform to a bottom in a housing of the optical measurement system.[Clause 15.] Method according to any embodiment disclosed in this application or according to any of the claims or clauses or according to clause 13 or 14, wherein aligning comprises aligning a mount that can hold a camera, wherein preferably aligning comprises providing an auxiliary alignment tool, such as a frosted plate having a hole, and mounting the auxiliary alignment tool in the mount that can hold the camera.[Clause 16.] Method according to any embodiment disclosed in this application or according to any of the claims or clauses or according to any of the clauses 13-15, wherein the method comprises positioning a camera on the optical platform before positioning the optical platform with aligned beam path in the optical measurement system, wherein preferably the method comprises providing the camera in a mount on the optical platform and wherein aligning comprises aligning the camera, wherein more preferably aligning comprises adjusting a position of the mount for the camera on the optical platform, wherein the method preferably comprises positioning one or more shrouds on the optical platform to surround at least partially the aligned beam path. [Clause 17.] Kit-of-parts for an optical platform for, preferably being releasably positionable within a housing of, an optical measurement system that has a cantilever, the kit comprising at least: a base a mount for a camera one or more optical devices for guiding an optical beam wherein preferably the kit has any of the features provided in the clauses and / or in the description and / or in the claims.

Claims

CLAIMS1. Optical measurement device for performing measurements on a sample, comprising: a housing; an XY-stage having a sample holder, mounted in the housing, wherein the sample holder is configured to hold the sample; a cantilever, connected to an optical waveguide, the cantilever mounted on one side of the XY-stage in the housing; and a camera, mounted opposite the one side of the XY-stage in the housing, the camera arranged for imaging the sample, wherein the camera is mounted on an optical platform that is removably fixed in the housing.

2. Optical measurement system according to claim 1 , wherein the optical waveguide comprises an optical fiber, wherein the cantilever is positioned at an end of the optical fiber, wherein preferably the cantilever is incorporated in the end of the optical fiber and / or an electromagnetic radiation detector is connected to the other end of the optical fiber.

3. Optical measurement system according to any of the previous claims, wherein the optical platform comprises a mount for the camera, wherein preferably the mount for the camera is a camera position adjustment mount for adjusting the camera position, wherein more preferably the camera position adjustment mount comprises a motor for adjusting the camera position.

4. Optical measurement system according to any of the previous claims, wherein the optical platform comprises one or more optical devices removably mounted on the optical platform wherein preferably the one or more optical devices comprise one or more mirrors mounted on the optical platform, preferably comprising at least one folding mirror, wherein preferably the folding mirror is mounted to reflect electromagnetic radiation directed generally towards the optical platform to generally parallel on the optical platform, wherein preferably the one or more mirrors are mounted on one or more mirror adjustment mounts, wherein preferably the mirror adjustment mount has one or more clips for mounting a mirror and / or has one or more adjustable mirror support pins, wherein more preferably the mirror adjustment mount comprises a motor for adjusting the mirror position, wherein the optical platform has one or more shrouds, preferably positioned between mirrors of the optical platform and / or positioned between a mirror and the camera mount.

5. Optical measurement system according to claim 3 or 4, wherein the optical platform comprises a mount for temporarily mounting an electromagnetic radiation source, wherein preferably the mount for temporally mounting the electromagnetic radiation source is arranged to mount the electromagnetic radiation source to radiate generally towards, preferably perpendicular to, the optical platform.

6. Optical measurement system according to any of the previous claims, wherein the housing comprises, in a bottom part, a closeable door for loading and unloading the optical platform into and out of the housing; and / or the housing comprises, near a bottom part, at least one guide for the optical platform and at least one or more stops for the optical platform; and / or the housing comprises one or more openings for additional / other light sources; and / or the housing comprises one or more openings occupied by cables needed for the functioning of the camera.

7. Optical measurement system according to any of the previous claims, wherein an objective is mounted in the housing in an electromagnetic radiation path between the XY stage and the optical platform; and / or the cantilever is mounted on a Z-stage; and / or the cantilever is mounted on a fine-motion Z-stage attached to a coarse Z-stage; and / or the sample holder is configured to receive one or more well plates. a light source is configured to provide light from the cantilever side, a light source is configured to provide light from the optical platform side.

8. Optical platform for being releasably positionable within a housing of an optical measurement system with a cantilever, wherein the optical platform comprises: a base, a mount for an optical source that directs a beam generally towards the base, a mount for a camera, and one or more optical devices, preferably mirrors and / or lenses, for guiding the beam from the mount for the optical source to the mount for the camera, wherein at least a part of the beam is guided generally parallel to the base.

9. Optical platform for being releasably positionable within a housing of an optical measurement system with a cantilever, wherein the optical platform comprises: a base, a camera held by a mount for a camera, the mount for the camera connected to the base, and one or more optical devices for guiding electromagnetic radiation to the camera, wherein the mount for the camera is a camera position adjustment mount.

10. Optical platform according to claim 8, further comprising a mount for a camera that holds a camera, wherein the mount for the camera connected to the base, and one or more optical devices for guiding electromagnetic radiation to the camera, wherein the mount for the camera is a camera position adjustment mount,OR optical platform according to claim 9, further comprising a mount for an optical source that directs a beam generally towards the base, a mount for a camera, and one or more optical devices, preferably mirrors and / or lenses, for guiding the beam from the mount for the optical source to the mount for the camera, wherein at least a part of the beam is guided generally parallel to the base.

11. Optical platform according to any of the claims 8-10, wherein the optical platform has a positioning system, preferably a locking system, for positioning the optical platform, preferably positioning the base, in a predetermined position within the housing, preferably onto a bottom frame, of the optical measurement system with the cantilever.

12. Optical platform according to any of the claim 8-11 , wherein at least one of the optical devices is a folding mirror, wherein preferably at least one mirror is arranged to reflect electromagnetic radiation generally directed at the base into generally directed parallel to the base, a dichroic mirror is mounted on the base of the platform, the one or more optical devices comprise one or more mirrors, wherein at least one mirror is mounted on mirror adjustment mounts, preferably held by one or more clips and more preferably supported by one or more adjustable pins.

13. Method for aligning a beam path of an optical platform for viewing samples held by an XY-stage in an optical measurement system that has a cantilever, wherein the method comprises: simulating a beam path of the optical platform; aligning the beam path of the optical platform using the simulated beam path, and positioning the optical platform with aligned beam path in the optical measurement system.

14. Method according to claim 13, wherein: simulating a beam path comprises mounting a laser on an optical platform, and removing the laser is removed before position the optical platform in the optical measurement system, wherein preferably the laser is mounted in a bracket mounted on the optical platform, and / or the method comprises mounting one or more mirrors on the optical platform in the beam path and wherein aligning comprises adjusting the one or more mirrors mounted on the optical platform, and / or positioning the optical platform with aligned beam path in the optical measurement system comprises:o opening and closing a door of a housing of the optical measurement system, and / or o aligning a position of the optical platform in the optical measurement system by providing alignment bumpers in the housing of the optical measurement system, and / or o fixing the aligned optical platform to a bottom in a housing of the optical measurement system.

15. Method according to claim 13 or 14, wherein aligning comprises aligning a mount that can hold a camera, wherein preferably aligning comprises providing an auxiliary alignment tool, such as a frosted plate having a hole, and mounting the auxiliary alignment tool in the mount that can hold the camera.

16. Method according to any of the claims 13-15 wherein the method comprises positioning a camera on the optical platform before positioning the optical platform with aligned beam path in the optical measurement system, wherein preferably the method comprises providing the camera in a mount on the optical platform and wherein aligning comprises aligning the camera, wherein more preferably aligning comprises adjusting a position of the mount for the camera on the optical platform, wherein the method preferably comprises positioning one or more shrouds on the optical platform to surround at least partially the aligned beam path.

17. Kit-of-parts for an optical platform for being releasably positionable within a housing of an optical measurement system that has a cantilever, the kit comprising at least: a base a mount for a camera one or more optical devices for guiding an optical beam wherein preferably the kit has any of the features provided in the clauses and / or in the description.

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