WO2009040745A1 - Objective driving unit for an optical device - Google Patents
Objective driving unit for an optical device Download PDFInfo
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- WO2009040745A1 WO2009040745A1 PCT/IB2008/053885 IB2008053885W WO2009040745A1 WO 2009040745 A1 WO2009040745 A1 WO 2009040745A1 IB 2008053885 W IB2008053885 W IB 2008053885W WO 2009040745 A1 WO2009040745 A1 WO 2009040745A1
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- WIPO (PCT)
- Prior art keywords
- objective
- optical device
- actuator head
- axial direction
- optical
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Classifications
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- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B26/00—Optical devices or arrangements for the control of light using movable or deformable optical elements
- G02B26/08—Optical devices or arrangements for the control of light using movable or deformable optical elements for controlling the direction of light
- G02B26/0875—Optical devices or arrangements for the control of light using movable or deformable optical elements for controlling the direction of light by means of one or more refracting elements
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- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B26/00—Optical devices or arrangements for the control of light using movable or deformable optical elements
- G02B26/08—Optical devices or arrangements for the control of light using movable or deformable optical elements for controlling the direction of light
- G02B26/10—Scanning systems
- G02B26/101—Scanning systems with both horizontal and vertical deflecting means, e.g. raster or XY scanners
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- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B21/00—Microscopes
- G02B21/0004—Microscopes specially adapted for specific applications
- G02B21/002—Scanning microscopes
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- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B7/00—Mountings, adjusting means, or light-tight connections, for optical elements
- G02B7/003—Alignment of optical elements
- G02B7/005—Motorised alignment
Definitions
- the invention relates to an objective driving unit for an optical device.
- An optical scanning microscope is used to image a sample by scanning a focused spot of light across the sample and collecting, on a detector, the light interacted (for instance, reflected or scattered) by the sample.
- the spot is focused on the sample by a microscope objective.
- Fig.l are schematically represented the main parts of a microscope of the prior art.
- Light is emitted by a light source 1, preferably a laser diode.
- the emitted beam of light 2 is reflected at a beam splitter 3 and converged into a parallel beam of light 5 by a collimator lens 4 centered on the optical axis z of the microscope.
- An objective lens 6 focuses the parallel light beam 5 into a tiny spot at position 7 that is incident on the sample 8.
- Light interacted by the sample 8 is captured by the objective lens 6 and ends up, via the collimator lens 4 and the beam splitter 3, on a detector 9, preferably a silicon photo-diode.
- the scanning microscope comprises means (not drawn on Fig.
- the means for displacing the focused spot 7 in the transverse directions x, y may comprises, for instance, a scanning mirror placed in the path of the incident parallel light beam 5 which, in this case, will be a two-parts path, to and from the mirror.
- the means for displacing the focused spot 7 may comprise an actuator for displacing the objective lens 6.
- the microscope has to comprise two independent means for laterally displacing the focused spot.
- US 2002/0018291 discloses a microscope comprising an inner frame, which elastically holds an actuator head through two sets of spiral plate springs, arranged in parallel, and regulates the movement of the actuator head so that it can be moved in a Z direction only.
- the actuator head has an aperture for an optical path.
- the actuator head elastically holds an objective frame through four bar- shaped parallel springs, each made with an elastic body, and regulates the movement of the objective frame so that it can be moved in an XY direction with respect to the intermediate support. Consequently, the objective frame and the objective lens fixed thereto, although not moved in the direction of rotation with respect to the inner frame, is elastically held so that they can be freely moved in a direction.
- the inner frame has two voice coil motors for driving the objective frame in the XZ direction and two voice coil motors for driving the objective frame in the YZ direction.
- the voice coil motors are biaxial actuators of the same structure which are different in direction of mounting to the inner frame from each other. Each of them is constructed with a permanent magnet, a yoke, two Z-direction driving coils, and an X- or Y-direction horizontal driving coil.
- the optical device further comprising second driving means (24a, 24b, 28a,
- translating the actuator head in the transverse directions simultaneously translates the objective holder and the first driving means.
- the objective holder can be translated independently in the axial direction via the first driving means.
- the driving means can be driven quickly for 3D scanning or positioning, while consuming less electrical power than the prior art driving means. This is notably due to the fact that the arrangement of the invention avoids the mechanical resistance of the spiral plate springs and the bar- shapes hinges along the optical axis.
- the optical device further comprises a frame supporting the actuator head, along the axial direction and with two degrees of freedom in the transverse directions, through bar-shaped hinges extending substantially in the axial direction and having only elastic properties in a plane parallel to the transverse directions.
- the second driving means are interposed between the actuator head and the frame for translating the actuator head in the transverse directions.
- the optical device comprises connecting means adapted to connect the objective holder to the actuator head in a fixed manner in the transverse directions and elastically in the axial direction.
- the connecting means form a membrane.
- first and/or second driving means comprise electromagnetical motors, for instance voice coil motors.
- the optical device comprises an objective supported by the objective holder and comprising a single plastic lens or a diffractive optical element.
- the actuator head comprises a wall defining a room into which the objective holder and the first driving means are at least partially enclosed.
- the wall of actuator head and the objective holder have generally a coaxial cylindrical shape.
- the optical device comprises a tilting mirror placed in the optical axis and substantially in-between the bar hinges.
- the optical device is an optical scanning microscope, a microdissection device or an optical tweezers.
- - Fig.l is a schematic block diagram of the main parts of a microscope of the prior art
- FIG.2 is a perspective view of an embodiment of an optical scanning microscope according to the invention.
- - Fig.3 is a cross-section side view of the microscope of Fig.2 and
- - Fig.4 is a cross-section side view of a second embodiment of a microscope according to the invention.
- the optical device 10 of an optical scanning microscope comprises an objective 11, having an optical axis z which defines an axial direction z.
- Two transverse directions x, y, i.e. perpendicular to each other, are defined here-after normal to the optical axis.
- An objective it should be understood any optical device adapted to optically guide light beams to or from a sample.
- An objective may comprise a single objective lens or a plurality of objective lenses, such as a doublet of lenses or more complicated combinations of lenses.
- An objective may also comprise a diffractive optical element; a diffractive optical element is a component that diffracts light into a set of diffraction orders, the amplitudes and phases of these orders being designed to generate a required light distribution in the sample plane.
- An objective in any case presents a global optical axis for the light beams passing through.
- the objective comprises a single lens 11.
- the optical device 10 also comprises an objective holder 12, for supporting the objective 11, preferably in a fixed (interdependent) manner. Since, in the embodiment described, the objective is a lens 11, the objective holder 12 is a lens holder 12.
- the lens holder 12 is herein of a substantially cylindrical shape around the axial direction z and more precisely of a tubular shape. It supports the lens 11 on its upper extremity. On its lower extremity, the lens holder 12 supports fixedly a balancing plate 13, which function is to balance (compensate for) the weight of the lens 11 on the upper extremity.
- the optical device 10 comprises an actuator head 14 which comprises the lens holder and first driving means which will described herein-after.
- the actuator head 14 comprises a wall 14w defining a room, or in other words an interior volume, the lens holder 12 being at least partly contained within this volume.
- the actuator head 14 and the lens holder 12 are coaxial.
- the lens holder 12 is almost totally contained within the volume of the actuator head 14.
- the lens holder 12 is held in place along the transverse directions (x, y) but has a degree of freedom in the axial direction z.
- the lens holder 12 is connected to the actuator head 14 by connecting means 15 allowing relative movement in the axial direction z, at least in a certain range.
- the connecting means and the actuator together supports the objective holder.
- the connecting means comprise two elastic membranes 15a, 15b, an upper membrane 15a and a lower membrane 15b, respectively provided between the respective upper and lower extremities of the lens holder 12 and of the actuator head 14.
- the membranes 15a, 15b are adapted to connect the lens holder 12 to the actuator head 14 in a fixed manner in the transverse directions x, y and elastically in the axial direction z.
- each membranes 15a, 15b comprises a disc with a hole in the middle for connection to the lens holder 12, the full part of the disc being provided with cutouts 16 which allow an elastic deformation of the membranes 15 a, 15b in the axial direction z.
- Any other suitable means can be contemplated, for instance spiral plate springs.
- the membranes 15a, 15b fulfill a spring function and the lens holder 12 has a degree of freedom in the axial direction z relatively to the actuator head 14.
- the lens holder 12 can therefore be driven in line with the optical axis z and keep relative high stiffness in the plane perpendicular to the optical axis z.
- a force may be applied to move the lens holder 12 relatively to the actuator head 14 in the axial direction z, but if this force is stopped, the lens holder 12 will come back to its original position because of the spring effect of the membranes.
- the objective driving unit 10 comprises driving means 17 interposed between the actuator head 14 and the objective holder 12 for translating the objective holder 12 in the axial direction z, relatively to the actuator head 14.
- the driving means may be designated as focus driving means 17, since they permit translating the objective lens
- the driving means 17 are provided within said inner volume of the actuator head 14 and are connected to the lens holder 12 and to the actuator head 14, for driving in translation along the axial direction z the lens holder 12 relatively to the actuator head 14.
- the driving means 17 are provided between the upper and lower membranes 15a, 15b, in the embodiment described, in the middle in between the membranes 15a, 15b.
- the driving means 17 comprise an actuator 17, which will be referred to as the z-actuator 17, since it induces a translation movement in the axial direction z.
- the z-actuator 17 is, in the embodiment described, an electromagnetic motor known as a voice coil motor. It comprises a driving coil 18, fixed to the lens holder 12 and kept in position between two transversally extending flanges 19a, 19b of the exterior surface of the lens holder 12, and permanents magnets 20, fixed to the actuator head 14, to its interior surface, and facing the coil 18. By sending current in the driving coil 18, a translation movement is obtained because of changes in the magnetic field between the coil 18 and the permanent magnets 20. Voice coil motors are well known in the art and do not need to be described in details.
- the optical device 10 further comprises a frame 21, which is a structure adapted to be fixed in position to the microscope and which supports the actuator head 14 with a degree of freedom in the two transverse directions x, y but not in the axial direction z.
- the actuator head 14 can therefore be driven in translation along each of the transverse directions x, y.
- the frame 21 here comprises four vertical posts 21a, 21b, 21c, 21 d fixed on a horizontal support plate 21 e.
- the frame 21 is therefore intended to become part of the structure of the microscope 21 and forms a structural link between the actuator head 14 and the fixed structure of the microscope. With its frame 21, the optical device 10 forms a module that may easily be integrated and fixed to a wide range of optical systems.
- the optical device 10 comprises driving means 24a, 24b, 28a, 28b interposed between the frame 21 and the actuator head 14, for translating the actuator head 14 in the transverse directions x, y, relatively to the frame 21.
- the actuator head 14 is supported by the frame 21 through bar- shaped hinges 23 extending substantially along the axial direction (z).
- each bar-shaped hinge is fixed to the horizontal support plate 21e of the frame 21, while the other extremity is fixed to the wall of the actuator head via any connecting means known in the art.
- Those bar-shapes hinges 23 have elastic properties so that they permit translation of the actuator head 14 in the transverse direction x, y but not in the axial direction z (unless little axial movements induced by the movements in the transverse directions x, y, the compensation of which will be explained below).
- the microscope comprises four bar-shaped hinges 23 spatially distributed around the optical axis (z).
- the driving means 24, 28 comprise, in the embodiment described, two actuators, one for each transverse direction x, y.
- the actuator driving the actuator head 14 in translation in the x-direction will be designated as the x-actuator.
- the actuator driving the actuator head 14 in translation in the y-direction will be designated as the y-actuator.
- the x-actuator 24 comprises two voice coil motors 24a, 24b, placed on opposite sides, in the x-direction, of the actuator head 14.
- the x-actuator's voice coil motors 24a, 24b each comprise a coil 25a, 25b, fixed to the actuator head 14, and a permanent magnet 26a, 26b, fixed to the frame 21 and facing the corresponding coil 25a, 25b.
- Each permanent magnet 26a, 26b is fixed to a corresponding post 21a, 21c of the frame 21, respectively.
- a yoke 27a, 27b is provided around each voice coil motor 24a, 24b, for guiding and shielding the magnetic field in order to get a stronger magnetic field. Such yokes 27a, 27b are well known in the art.
- the permanent magnets 26a, 26b support a plate 26a', 26b', respectively, for guiding the flux lines to the yoke 27a, 27b, as well known in the art.
- the shape of the coils 25a, 25b and yokes 27a, 27b is not round, as in classical voice coil motors, but oval. Such an oval shape provides a larger stroke to the motors 24a, 24b; the horizontal width of the coils 25 a, 25b sets the maximum movement while the vertical width is less than the horizontal one for efficiency reasons.
- the y-actuator 28 comprises two voice coil motors 28a, 28b, placed on opposite sides, in the y-direction, of the actuator head 14.
- the y-actuator's voice coil motors 28a, 28b are similar to the x-actuator's voice coil motors 24a, 24b and will not be described in details.
- the x-actuator 24 and the y-actuator 28 permit to drive the actuator head 14 in translation in the transverse directions x, y and therefore to drive the objective holder 12 in those transverse directions x, y, since the objective holder 12 is connected to the actuator head 14 with only a degree of freedom in the axial direction z, hence being interdependent in the transverse directions x, y.
- the objective lens 11, fixed on the lens holder 12 can be driven in three dimensions, along the axial direction with the driving means 17 interposed between the actuator head 14 and the objective holder 12 and along the transverse directions x, y with the driving means 24a, 24b 28a, 28b interposed between the frame 21 and the actuator head 14.
- the focused spot may suffer little movements in the axial direction z, which effect is known as defocus.
- the relation between the translation in the transverse directions x, y of the actuator head 14 and this defocus effect is known.
- Focusing may be performed in a closed loop servo system so that this correction is automatically done.
- the microscope of the invention makes it possible to scan a sample in different sections in depth, since the focused spot may be displaced in the three dimensions by the means 17, 24a, 24b, 28a, 28b driving the objective lens 11.
- a clean three-dimensional image of the sample may be constructed.
- the position of the objective in relation to the sample has to be known, in order to restore a true image out of the gathered information on the sample and, notably, not to have distortions in the image.
- a closed loop servo controlled system may be provided for the driving means 17, 24a, 24b, 28a, 28b, as known in the art.
- scanning may either be obtained by stepwise or continuous displacement of the objective.
- the microscope has been presented in relation with an objective situated on the upper part of the microscope, its optical axis extending along the vertical direction; such a configuration provides an advantage as to gravity issues.
- the microscope may be orientated in another direction.
- the optical scanning microscope comprises a light objective comprising plastic lenses; even faster driving of the objective can therefore be obtained, since plastic lenses are very light.
- the objective may comprise a single plastic lens.
- the light source for irradiating the sample may be placed below the objective 11, the sample being positioned opposite this light source, in line with the optical axis z.
- the light source is not situated in the optical axis of the objective. This permits to solve some access issues.
- the light therefore has to be directed from the light source towards the objective.
- a mirror 29 can be placed to deviate a light beam into the direction of the objective 11, along the optical axis z.
- the mirror 29 is a tilting mirror 29, interdependent with permanent magnets 30 fixed on the periphery of the mirror 29 and facing a coil 31 for driving the movement of the mirror 29.
- This mirror is arranged in between the posts 21 and, more preferably, centered with respect to the optical axis in-between the four bar-shaped hinges 23.
- the microscope comprises a light beam access 32, formed by a hole 32 in the frame 21 of the objective driving unit 10.
- the objective 11, the objective holder 12, the actuator head 14 and the driving means 17, 24a, 24b 28a, 28b may form an independent driving unit which may be used in several more complex optical devices, for example a scanning microscope such as the one already described but also any device where a light beam should be focused and displaced (e.g. scanned or positioned) on a sample, and comprising a structure where the driving unit may be fixed.
- the optical device is a microdissection device.
- the driving unit at least is used in a microdissection device.
- Laser microdissection is a method to cut out micron-sized to mm-sized tissue samples (e.g. individual cells) from a larger sample by the use of a focused laser beam, the larger sample being inspected under a microscope.
- Ablation of material along the cutting line is most effective when the absorption is relatively high. This can be achieved with ultraviolet light (wavelength less than about 400 nm, typically 350 nm).
- Removal of the cut-out tissue sample can be done in a number of ways. For instance, a contactless removal process may be performed, based on the use of a slightly de focused pulse of light generated with the same laser used for the cutting process to exert a force on the cut-out tissue sample, thus propelling it towards a collection basket.
- Disadvantages of the prior art microdissection devices mainly result in the conventional means to displace the focused spot in three dimensions (transverse dimensions x, y for tracing out the cutting line, direction of the optical axis z of the objective focusing the laser for focusing and defocusing).
- the microscope slide on which the object layer is deposited is generally mounted on a translation stage for displacing the object layer with respect to the focused spot or the focus knob of the microscope is used to displace the focused spot in the axial direction z.
- a known alternative consists in using beam deflection means, for example tilting mirrors that can be used to change the angle at which the beam is incident on the objective and thus displace the focused spot in the field of the objective.
- beam deflection means for example tilting mirrors that can be used to change the angle at which the beam is incident on the objective and thus displace the focused spot in the field of the objective.
- such method may have a limited applicability, for instance when a singlet aspherical lens is used, as the field of such a lens is limited compared to the field of a conventional microscope objective.
- a method for laser microdissection on a device according to the invention comprise the following steps:
- the axial position is maintained by keeping the feedback system in closed loop.
- the driving signals for the x-actuator and the y-actuator are determined from a closed loop feedback system, i.e. they are constantly adapted to keep the actual positions values measured with a position sensor equal to the values corresponding to the boundaries of the imaged regions of interest.
- a closed loop feedback system has the advantage of suppressing disturbing effects of vibrations and frequency dependent transfer and delay effects related to friction and the inertia of the moving lens.
- the optical device of the invention can be a compact optical tweezers.
- Optical tweezers are well known in the art.
- the principle is optical trapping: a laser beam is incident on a particle through an objective lens so as to trap the particle in the focal region of the lens, provided that the so-called gradient force (pointing towards the maximum intensity at the focal point) can overcome the so-called scattering force (pointing away from the incident beam). Those gradient forces are induced by the laser beam.
- the numerical aperture of the lens is high enough, the force may be so high as to grab and move a particle or a group of particles.
- the typical range of size of particles that may be moved thanks to optical tweezers is nowadays from a few nanometers to a few tens of micrometers. For instance, those particles may be cells.
- a particle can thus be trapped in the region close to focus, the use of the objective driving unit in the optical tweezers allowing for further manipulation of the particle.
- optical tweezers device of the invention can be applied, in particular, to genomics, proteomics and single cell manipulation.
- a computer program may be stored/distributed on a suitable medium, such as an optical storage medium or a solid-state medium supplied together with or as part of other hardware, but may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunication systems. Any reference signs in the claims should not be construed as limiting the scope.
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Abstract
The invention relates to an optical device comprising an actuator head (14) which comprises: - an objective holder (12) for supporting an objective (11) having an optical axis aligned with an axial direction (z), and - first driving means (17) for translating the objective holder (12) in said axial direction (z), the optical device further comprising second driving means (24a, 24b, 28a, 28b) for translating the actuator head (14) in two transverse directions (x, y) being both perpendicular to the axial direction (z).
Description
Objective driving unit for an optical device
Field of the invention
The invention relates to an objective driving unit for an optical device.
Background of the invention An optical scanning microscope is used to image a sample by scanning a focused spot of light across the sample and collecting, on a detector, the light interacted (for instance, reflected or scattered) by the sample. The spot is focused on the sample by a microscope objective.
On Fig.l are schematically represented the main parts of a microscope of the prior art. Light is emitted by a light source 1, preferably a laser diode. The emitted beam of light 2 is reflected at a beam splitter 3 and converged into a parallel beam of light 5 by a collimator lens 4 centered on the optical axis z of the microscope. An objective lens 6 focuses the parallel light beam 5 into a tiny spot at position 7 that is incident on the sample 8. Light interacted by the sample 8 is captured by the objective lens 6 and ends up, via the collimator lens 4 and the beam splitter 3, on a detector 9, preferably a silicon photo-diode. The scanning microscope comprises means (not drawn on Fig. 1) for displacing the spot in the two directions x, y perpendicular to the optical axis z, that is say, the transverse directions x, y. The sample 8 is thereby scanned by the focused light spot 7. At each position of the focused light spot 7, an image of the interacted light spot is recorded on the detector 9, the focused light spot 7 is displaced to the next position and another image is recorded, etc. A complete image of the sample 8 is obtained once all the required positions in the sample 8 have been imaged, by combining the recorded images into a complete image.
The means for displacing the focused spot 7 in the transverse directions x, y may comprises, for instance, a scanning mirror placed in the path of the incident parallel light beam 5 which, in this case, will be a two-parts path, to and from the mirror. According to another solution, the means for displacing the focused spot 7 may
comprise an actuator for displacing the objective lens 6. As there are two independent transverse directions x, y to be scanned, the microscope has to comprise two independent means for laterally displacing the focused spot. These means can be any of the above mentioned examples, a combination or any other embodiment not mentioned.
It may however also be interesting to be able to displace the objective along the optical axis z of the microscope, to fulfill a focus function and be able to scan different depths of the sample 8.
US 2002/0018291 discloses a microscope comprising an inner frame, which elastically holds an actuator head through two sets of spiral plate springs, arranged in parallel, and regulates the movement of the actuator head so that it can be moved in a Z direction only. The actuator head has an aperture for an optical path. The actuator head elastically holds an objective frame through four bar- shaped parallel springs, each made with an elastic body, and regulates the movement of the objective frame so that it can be moved in an XY direction with respect to the intermediate support. Consequently, the objective frame and the objective lens fixed thereto, although not moved in the direction of rotation with respect to the inner frame, is elastically held so that they can be freely moved in a direction. The inner frame has two voice coil motors for driving the objective frame in the XZ direction and two voice coil motors for driving the objective frame in the YZ direction. The voice coil motors are biaxial actuators of the same structure which are different in direction of mounting to the inner frame from each other. Each of them is constructed with a permanent magnet, a yoke, two Z-direction driving coils, and an X- or Y-direction horizontal driving coil.
While the microscope of Fig.l has been presented in relation with an objective comprising a single lens, optical scanning microscopes may also have an expensive and complex objective with relatively large mass and dimensions. Fast scanning and focusing movements of the objective are in any case very hard to obtain and the means for displacing the objectives should be very strong, consume a lot of power and have large dimensions, especially if three-dimensional (3D) scanning of the spot is required. This is the case for the microscope of US 2002/0018291 where, notably for driving the objective frame in the direction of the optical axis, the voice coil motors have to counteract a force generated by the bar-shaped parallel springs,
which are linked to the spiral plate springs in turn connected to the inner frame. As a consequence, the motors consume a lot of electric power. This is a disadvantage, all the more since high electrical power motor have to be oversized, resulting in a non compact and slow (not to say static) assembly. The same problems occur in any optical device, comprising an objective through which a light spot is illuminated onto an object and has to be displaced (e.g. scanned or positioned) in 3D. For instance, this applies to optical tweezers or microdissection devices.
Summary of the invention
It is therefore an object of the present invention to provide driving means for 3D displacement of the light spot of an optical device that are cheap, small in size, lightweight suitable for different applications and not consuming too much power.
In accordance with the present invention there is provided an optical device comprising an actuator head (14) which comprises:
- an objective holder (12) for supporting an objective (11) having an optical axis aligned with an axial direction (z), and
- first driving means (17) for translating the objective holder (12) in said axial direction (z), the optical device further comprising second driving means (24a, 24b, 28a,
28b) for translating the actuator head (14) in two transverse directions (x, y) being both perpendicular to the axial direction (z).
Thus, according to the invention, translating the actuator head in the transverse directions, simultaneously translates the objective holder and the first driving means.
And, while the actuator head is translated, the objective holder can be translated independently in the axial direction via the first driving means. Such an arrangement allows for a very compact configuration. Further, the driving means can be driven quickly for 3D scanning or positioning, while consuming less electrical power than the prior art driving means.
This is notably due to the fact that the arrangement of the invention avoids the mechanical resistance of the spiral plate springs and the bar- shapes hinges along the optical axis.
According to an embodiment, the optical device further comprises a frame supporting the actuator head, along the axial direction and with two degrees of freedom in the transverse directions, through bar-shaped hinges extending substantially in the axial direction and having only elastic properties in a plane parallel to the transverse directions.
According to an embodiment, the second driving means are interposed between the actuator head and the frame for translating the actuator head in the transverse directions.
According to an embodiment, the optical device comprises connecting means adapted to connect the objective holder to the actuator head in a fixed manner in the transverse directions and elastically in the axial direction. According to an embodiment, the connecting means form a membrane.
According to an embodiment the first and/or second driving means comprise electromagnetical motors, for instance voice coil motors.
According to an embodiment the optical device comprises an objective supported by the objective holder and comprising a single plastic lens or a diffractive optical element.
According to an embodiment, the actuator head comprises a wall defining a room into which the objective holder and the first driving means are at least partially enclosed.
According to an embodiment, the wall of actuator head and the objective holder have generally a coaxial cylindrical shape.
According to an embodiment the optical device comprises a tilting mirror placed in the optical axis and substantially in-between the bar hinges.
According to an embodiment, the optical device is an optical scanning microscope, a microdissection device or an optical tweezers. These and other aspects of the invention will be more apparent from the following description with reference to the attached drawings.
Brief description of the drawings
- Fig.l is a schematic block diagram of the main parts of a microscope of the prior art;
- Fig.2 is a perspective view of an embodiment of an optical scanning microscope according to the invention;
- Fig.3 is a cross-section side view of the microscope of Fig.2 and
- Fig.4 is a cross-section side view of a second embodiment of a microscope according to the invention.
Detailed description of the embodiments
With reference to Figs.2 and 3, the optical device 10 of an optical scanning microscope according to a first embodiment of the invention comprises an objective 11, having an optical axis z which defines an axial direction z. Two transverse directions x, y, i.e. perpendicular to each other, are defined here-after normal to the optical axis. By an "objective", it should be understood any optical device adapted to optically guide light beams to or from a sample. An objective may comprise a single objective lens or a plurality of objective lenses, such as a doublet of lenses or more complicated combinations of lenses. An objective may also comprise a diffractive optical element; a diffractive optical element is a component that diffracts light into a set of diffraction orders, the amplitudes and phases of these orders being designed to generate a required light distribution in the sample plane. An objective in any case presents a global optical axis for the light beams passing through. In the embodiment described, the objective comprises a single lens 11.
The optical device 10 also comprises an objective holder 12, for supporting the objective 11, preferably in a fixed (interdependent) manner. Since, in the embodiment described, the objective is a lens 11, the objective holder 12 is a lens holder 12. The lens holder 12 is herein of a substantially cylindrical shape around the axial direction z and more precisely of a tubular shape. It supports the lens 11 on its upper extremity. On its lower extremity, the lens holder 12 supports fixedly a balancing plate 13, which function is to balance (compensate for) the weight of the lens 11 on the upper extremity.
The optical device 10 comprises an actuator head 14 which comprises the lens holder and first driving means which will described herein-after.
In this embodiment, the actuator head 14 comprises a wall 14w defining a room, or in other words an interior volume, the lens holder 12 being at least partly contained within this volume.
This allows compactness of the microscope.
The actuator head 14 and the lens holder 12 are coaxial.
In the embodiment described, and for much compactness, the lens holder 12 is almost totally contained within the volume of the actuator head 14. The lens holder 12 is held in place along the transverse directions (x, y) but has a degree of freedom in the axial direction z.
In order to allow the axial direction degree of freedom of the lens holder 12 relatively to the actuator head 14, the lens holder 12 is connected to the actuator head 14 by connecting means 15 allowing relative movement in the axial direction z, at least in a certain range.
Thus, the connecting means and the actuator together supports the objective holder.
In the embodiment described, the connecting means comprise two elastic membranes 15a, 15b, an upper membrane 15a and a lower membrane 15b, respectively provided between the respective upper and lower extremities of the lens holder 12 and of the actuator head 14. The membranes 15a, 15b are adapted to connect the lens holder 12 to the actuator head 14 in a fixed manner in the transverse directions x, y and elastically in the axial direction z. For this purpose, each membranes 15a, 15b comprises a disc with a hole in the middle for connection to the lens holder 12, the full part of the disc being provided with cutouts 16 which allow an elastic deformation of the membranes 15 a, 15b in the axial direction z. Any other suitable means can be contemplated, for instance spiral plate springs.
The membranes 15a, 15b fulfill a spring function and the lens holder 12 has a degree of freedom in the axial direction z relatively to the actuator head 14. The lens holder 12 can therefore be driven in line with the optical axis z and keep relative high stiffness in the plane perpendicular to the optical axis z. A force may be applied to move the lens holder 12 relatively to the actuator head 14 in the axial direction z, but if
this force is stopped, the lens holder 12 will come back to its original position because of the spring effect of the membranes.
The objective driving unit 10 comprises driving means 17 interposed between the actuator head 14 and the objective holder 12 for translating the objective holder 12 in the axial direction z, relatively to the actuator head 14. The driving means may be designated as focus driving means 17, since they permit translating the objective lens
11 in the direction of its optical axis z.
The driving means 17 are provided within said inner volume of the actuator head 14 and are connected to the lens holder 12 and to the actuator head 14, for driving in translation along the axial direction z the lens holder 12 relatively to the actuator head 14. The driving means 17 are provided between the upper and lower membranes 15a, 15b, in the embodiment described, in the middle in between the membranes 15a, 15b.
The driving means 17 comprise an actuator 17, which will be referred to as the z-actuator 17, since it induces a translation movement in the axial direction z. The z-actuator 17 is, in the embodiment described, an electromagnetic motor known as a voice coil motor. It comprises a driving coil 18, fixed to the lens holder 12 and kept in position between two transversally extending flanges 19a, 19b of the exterior surface of the lens holder 12, and permanents magnets 20, fixed to the actuator head 14, to its interior surface, and facing the coil 18. By sending current in the driving coil 18, a translation movement is obtained because of changes in the magnetic field between the coil 18 and the permanent magnets 20. Voice coil motors are well known in the art and do not need to be described in details. The use of a voice coil motor permits a compact configuration. The optical device 10 further comprises a frame 21, which is a structure adapted to be fixed in position to the microscope and which supports the actuator head 14 with a degree of freedom in the two transverse directions x, y but not in the axial direction z. The actuator head 14 can therefore be driven in translation along each of the transverse directions x, y. The frame 21 here comprises four vertical posts 21a, 21b, 21c, 21 d fixed on a horizontal support plate 21 e.
The frame 21 is therefore intended to become part of the structure of the microscope 21 and forms a structural link between the actuator head 14 and the fixed
structure of the microscope. With its frame 21, the optical device 10 forms a module that may easily be integrated and fixed to a wide range of optical systems.
The optical device 10 comprises driving means 24a, 24b, 28a, 28b interposed between the frame 21 and the actuator head 14, for translating the actuator head 14 in the transverse directions x, y, relatively to the frame 21.
The actuator head 14 is supported by the frame 21 through bar- shaped hinges 23 extending substantially along the axial direction (z).
More precisely, an extremity of each bar-shaped hinge is fixed to the horizontal support plate 21e of the frame 21, while the other extremity is fixed to the wall of the actuator head via any connecting means known in the art. Those bar-shapes hinges 23 have elastic properties so that they permit translation of the actuator head 14 in the transverse direction x, y but not in the axial direction z (unless little axial movements induced by the movements in the transverse directions x, y, the compensation of which will be explained below). In the embodiment notably shown in figure 2, the microscope comprises four bar-shaped hinges 23 spatially distributed around the optical axis (z).
The driving means 24, 28 comprise, in the embodiment described, two actuators, one for each transverse direction x, y. The actuator driving the actuator head 14 in translation in the x-direction will be designated as the x-actuator. The actuator driving the actuator head 14 in translation in the y-direction will be designated as the y-actuator.
The x-actuator 24 comprises two voice coil motors 24a, 24b, placed on opposite sides, in the x-direction, of the actuator head 14. The x-actuator's voice coil motors 24a, 24b each comprise a coil 25a, 25b, fixed to the actuator head 14, and a permanent magnet 26a, 26b, fixed to the frame 21 and facing the corresponding coil 25a, 25b. Each permanent magnet 26a, 26b is fixed to a corresponding post 21a, 21c of the frame 21, respectively. A yoke 27a, 27b is provided around each voice coil motor 24a, 24b, for guiding and shielding the magnetic field in order to get a stronger magnetic field. Such yokes 27a, 27b are well known in the art. The permanent magnets 26a, 26b support a plate 26a', 26b', respectively, for guiding the flux lines to the yoke 27a, 27b, as well known in the art. As can be seen on Fig. 2, the shape of the coils 25a, 25b and yokes 27a, 27b is not round, as in classical voice coil motors, but oval. Such
an oval shape provides a larger stroke to the motors 24a, 24b; the horizontal width of the coils 25 a, 25b sets the maximum movement while the vertical width is less than the horizontal one for efficiency reasons.
Similarly, the y-actuator 28 comprises two voice coil motors 28a, 28b, placed on opposite sides, in the y-direction, of the actuator head 14. The y-actuator's voice coil motors 28a, 28b are similar to the x-actuator's voice coil motors 24a, 24b and will not be described in details.
The x-actuator 24 and the y-actuator 28 permit to drive the actuator head 14 in translation in the transverse directions x, y and therefore to drive the objective holder 12 in those transverse directions x, y, since the objective holder 12 is connected to the actuator head 14 with only a degree of freedom in the axial direction z, hence being interdependent in the transverse directions x, y.
Therefore, thanks to the structure of the optical device 10, the objective lens 11, fixed on the lens holder 12, can be driven in three dimensions, along the axial direction with the driving means 17 interposed between the actuator head 14 and the objective holder 12 and along the transverse directions x, y with the driving means 24a, 24b 28a, 28b interposed between the frame 21 and the actuator head 14.
When the objective lens 11 is translated in the transverse directions x, y, the focused spot may suffer little movements in the axial direction z, which effect is known as defocus. However, the relation between the translation in the transverse directions x, y of the actuator head 14 and this defocus effect is known. For this reason the defocus translation of the actuator head 14 can be corrected by the lens holder 12 being moved in translation along the optical axis z. Focusing may be performed in a closed loop servo system so that this correction is automatically done. The microscope of the invention makes it possible to scan a sample in different sections in depth, since the focused spot may be displaced in the three dimensions by the means 17, 24a, 24b, 28a, 28b driving the objective lens 11. By scanning many thin sections through the sample, a clean three-dimensional image of the sample may be constructed. During scanning the position of the objective in relation to the sample has to be known, in order to restore a true image out of the gathered information on the sample and, notably, not to have distortions in the image. For this purpose, a closed
loop servo controlled system may be provided for the driving means 17, 24a, 24b, 28a, 28b, as known in the art.
In the microscope of the invention, scanning may either be obtained by stepwise or continuous displacement of the objective. The microscope has been presented in relation with an objective situated on the upper part of the microscope, its optical axis extending along the vertical direction; such a configuration provides an advantage as to gravity issues. Of course, the microscope may be orientated in another direction.
According to a particular embodiment, the optical scanning microscope comprises a light objective comprising plastic lenses; even faster driving of the objective can therefore be obtained, since plastic lenses are very light. In particular, the objective may comprise a single plastic lens.
In the embodiment of the microscope which has been described with reference to Figs.2 and 3, the light source for irradiating the sample may be placed below the objective 11, the sample being positioned opposite this light source, in line with the optical axis z.
According to another embodiment, the light source is not situated in the optical axis of the objective. This permits to solve some access issues.
The light therefore has to be directed from the light source towards the objective. For this purpose, a mirror 29 can be placed to deviate a light beam into the direction of the objective 11, along the optical axis z.
Such an embodiment is represented on Fig.4. The already described elements of the microscopes are designated with the same reference numbers, since they are unchanged compared to the embodiment of Figs.2 and 3. According to this embodiment the mirror 29 is a tilting mirror 29, interdependent with permanent magnets 30 fixed on the periphery of the mirror 29 and facing a coil 31 for driving the movement of the mirror 29.
This mirror is arranged in between the posts 21 and, more preferably, centered with respect to the optical axis in-between the four bar-shaped hinges 23. An advantage of this latter configuration is compactness.
The microscope comprises a light beam access 32, formed by a hole 32 in the frame 21 of the objective driving unit 10. With such a configuration, a combination of
scanning by tilting the mirror 29, high frequently, and scanning the actuator head 14, relative low frequently, is possible.
In will be understood that the objective 11, the objective holder 12, the actuator head 14 and the driving means 17, 24a, 24b 28a, 28b may form an independent driving unit which may be used in several more complex optical devices, for example a scanning microscope such as the one already described but also any device where a light beam should be focused and displaced (e.g. scanned or positioned) on a sample, and comprising a structure where the driving unit may be fixed. Thus, according to an embodiment of the invention, the optical device is a microdissection device. In other words, the driving unit at least is used in a microdissection device.
Laser microdissection is a method to cut out micron-sized to mm-sized tissue samples (e.g. individual cells) from a larger sample by the use of a focused laser beam, the larger sample being inspected under a microscope. Ablation of material along the cutting line is most effective when the absorption is relatively high. This can be achieved with ultraviolet light (wavelength less than about 400 nm, typically 350 nm). Removal of the cut-out tissue sample can be done in a number of ways. For instance, a contactless removal process may be performed, based on the use of a slightly de focused pulse of light generated with the same laser used for the cutting process to exert a force on the cut-out tissue sample, thus propelling it towards a collection basket.
Disadvantages of the prior art microdissection devices mainly result in the conventional means to displace the focused spot in three dimensions (transverse dimensions x, y for tracing out the cutting line, direction of the optical axis z of the objective focusing the laser for focusing and defocusing). For example, in the state of the art, the microscope slide on which the object layer is deposited is generally mounted on a translation stage for displacing the object layer with respect to the focused spot or the focus knob of the microscope is used to displace the focused spot in the axial direction z. These methods have the disadvantage that a relatively large mass has to be displaced, resulting in slow scanning. A known alternative consists in using beam deflection means, for example tilting mirrors that can be used to change
the angle at which the beam is incident on the objective and thus displace the focused spot in the field of the objective. However, in certain applications, such method may have a limited applicability, for instance when a singlet aspherical lens is used, as the field of such a lens is limited compared to the field of a conventional microscope objective.
The above mentioned problems are all solved by the use of the optical device of the invention as a microdissection device. In particular, a single aspherical lens can be held in the lens holder 12. The focused spot can therefore be scanned in three dimensions in a fast manner. A method for laser microdissection on a device according to the invention comprise the following steps:
1. Taking an image of a tissue sample with the conventional microscope.
2. Identifying regions of interest by a trained operator or by an automated software routine. 3. Bringing the microdissection laser in focus by changing the axial position of the singlet aspherical lens, preferably by an automated routine that uses a closed loop feedback system. Such a system continuously adapts the driving signal corresponding to the axial position of the lens to keep a measured error signal equal to a given value. This error signal can be generated from a separate axial position sensor attached to the objective driving unit. Alternatively, it can be generated from the transmitted light captured by the microscope objective and imaged onto an electronic camera (e.g. minimizing spot size in the image), or from the reflected light captured by the optical system that produces the microdissection spot and imaged onto a photo- detector, preferably a quadrant photo-detector. During subsequent steps the axial position is maintained by keeping the feedback system in closed loop.
4. Tracing out the boundaries of the regions of interest by changing the transverse directions position of the singlet aspherical lens, thus doing the actual cutting out of the micro-samples. Similar to the axial position, the driving signals for the x-actuator and the y-actuator are determined from a closed loop feedback system, i.e. they are constantly adapted to keep the actual positions values measured with a position sensor equal to the values corresponding to the boundaries of the imaged regions of interest. Such a closed loop feedback system has the advantage of
suppressing disturbing effects of vibrations and frequency dependent transfer and delay effects related to friction and the inertia of the moving lens.
5. Removing the cut-out samples by the use of e.g. optical forces generated by the same beam or by the beam of a second laser, by gravity, or by other means. 6. Collecting the cut-out samples at a collection basket for further processing.
According to another embodiment the optical device of the invention can be a compact optical tweezers.
Optical tweezers are well known in the art. The principle is optical trapping: a laser beam is incident on a particle through an objective lens so as to trap the particle in the focal region of the lens, provided that the so-called gradient force (pointing towards the maximum intensity at the focal point) can overcome the so-called scattering force (pointing away from the incident beam). Those gradient forces are induced by the laser beam. If the numerical aperture of the lens is high enough, the force may be so high as to grab and move a particle or a group of particles. The typical range of size of particles that may be moved thanks to optical tweezers is nowadays from a few nanometers to a few tens of micrometers. For instance, those particles may be cells.
A particle can thus be trapped in the region close to focus, the use of the objective driving unit in the optical tweezers allowing for further manipulation of the particle.
The optical tweezers device of the invention can be applied, in particular, to genomics, proteomics and single cell manipulation.
Notably, the purity of the sample for molecular biological methods is of great importance. Small 'contaminations' can make it impossible to do a correct analysis. Microdissection allows for a simple and fast (non-contact) method for improving the quality of the sample.
While the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive; the invention is not limited to the disclosed embodiments.
Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, the disclosure, and the appended claims.
In the claims, the word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality. A single processor or other unit may fulfill the functions of several items recited in the claims.
The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. A computer program may be stored/distributed on a suitable medium, such as an optical storage medium or a solid-state medium supplied together with or as part of other hardware, but may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunication systems. Any reference signs in the claims should not be construed as limiting the scope.
Claims
1- Optical device comprising an actuator head (14) which comprises:
- an objective holder (12) for supporting an objective (11) having an optical axis aligned with an axial direction (z), and
- first driving means (17) for translating the objective holder (12) in said axial direction (z), the optical device further comprising second driving means (24a, 24b, 28a, 28b) for translating the actuator head (14) in two transverse directions (x, y) being both perpendicular to the axial direction (z).
2- Optical device according to claim 1, further comprising:
- a frame (21) supporting the actuator head (14), along the axial direction (z) and with two degrees of freedom in the transverse directions (x, y), through bar-shaped hinges (23) extending substantially in the axial direction (z) and having only elastic properties in a plane parallel to the transverse directions (x,y).
3- Optical device according to claim 2, the second driving means (24a, 24b, 28a, 28b) being interposed between the actuator head (14) and the frame (21) for translating the actuator head (14) in the transverse directions (x, y).
4- Optical device according to claim 1, comprising connecting means (15a, 15b) adapted to connect the objective holder (12) to the actuator head (14) in a fixed manner in the transverse directions (x, y) and elastically in the axial direction (z).
5. Optical device according to claim 4, the connecting means forming a membrane (15a, 15b).
6- Optical device according to claim 1, wherein the first and/or second driving means (17, 24a, 24b, 28a, 28b) comprise electromagnetical motors, for instance voice coil motors. 7- Optical device according to claim 1, further comprising an objective (11) supported by the objective holder and comprising a single plastic lens (11) or a diffractive optical element.
8- Optical device according to claim 1, wherein the actuator head comprises a wall defining a room into which the objective holder and the first driving means are at least partially enclosed.
9- Optical device according to claim 8, wherein the wall of actuator head (14) and the objective holder (12) have generally a coaxial cylindrical shape.
10- Optical device according to claim 2, further comprising a tilting mirror (29) placed in the optical axis and substantially in-between the bar hinges (23).
11- Optical scanning microscope or microdissection device or optical tweezers device according to claim 1.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP07301399 | 2007-09-26 | ||
| EP07301399.7 | 2007-09-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2009040745A1 true WO2009040745A1 (en) | 2009-04-02 |
Family
ID=40278797
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IB2008/053885 Ceased WO2009040745A1 (en) | 2007-09-26 | 2008-09-24 | Objective driving unit for an optical device |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2009040745A1 (en) |
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| WO2011098303A1 (en) * | 2010-02-12 | 2011-08-18 | Leica Microsystems Cms Gmbh | Device for scanning an object, method for operating the device and scanning microscope |
| EP3346288A1 (en) * | 2014-12-22 | 2018-07-11 | Google LLC | Time-of-flight camera system and method to improve measurement quality of weak field-of-view signal regions |
| EP3238432A4 (en) * | 2014-12-22 | 2018-08-01 | Google LLC | Integrated camera system having two dimensional image capture and three dimensional time-of-flight capture with movable illuminated region of interest |
| CN108599524A (en) * | 2018-05-15 | 2018-09-28 | 北京控制工程研究所 | A kind of flexible actuator of large stroke and high precision intelligence |
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| WO2011098303A1 (en) * | 2010-02-12 | 2011-08-18 | Leica Microsystems Cms Gmbh | Device for scanning an object, method for operating the device and scanning microscope |
| JP2013525823A (en) * | 2010-02-12 | 2013-06-20 | ライカ マイクロシステムス ツェーエムエス ゲーエムベーハー | Apparatus for scanning an object, method of operating the apparatus, and scanning microscope |
| US9036232B2 (en) | 2010-02-12 | 2015-05-19 | Leica Microsystems Cms Gmbh | Device for scanning an object, method for operating the device and scanning microscope |
| EP3346288A1 (en) * | 2014-12-22 | 2018-07-11 | Google LLC | Time-of-flight camera system and method to improve measurement quality of weak field-of-view signal regions |
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| US10055855B2 (en) | 2014-12-22 | 2018-08-21 | Google Llc | Time-of-flight camera system and method to improve measurement quality of weak field-of-view signal regions |
| US10181201B2 (en) | 2014-12-22 | 2019-01-15 | Google Llc | Time-of-flight camera system and method to improve measurement quality of weak field-of-view signal regions |
| CN108599524A (en) * | 2018-05-15 | 2018-09-28 | 北京控制工程研究所 | A kind of flexible actuator of large stroke and high precision intelligence |
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