WO2015167369A1

WO2015167369A1 - Object holder and microscope arrangement for positioning of the object holder

Info

Publication number: WO2015167369A1
Application number: PCT/SE2014/000055
Authority: WO
Inventors: Anders Rosenqvist
Original assignee: Teknikpatrullen Ab
Priority date: 2014-04-30
Filing date: 2014-04-30
Publication date: 2015-11-05

Abstract

In a combination of an object holder and an arrangement for one, two or three dimensional positioning of the object holder, the object holder comprises contact elements that are pairwise compatible with press elements of the arrangement, the contact elements can have flexible connections with an object space of the object holder and the press elements can have flexible connections with two to three actuators that have adjustable lengths along a first dimension. The arrangement can also be used for automatic handling of object holders, like for example lifting an object holder without any extra actuator.

Description

Title

Object holder and microscope arrangement for positioning of the object holder Technical Field

The present invention relates to an object holder and to an arrangement for positioning of the object holder in a microscope system. Background Art

Automatic microscope systems like for example the DM96 and DM1200 from CellaVision AB are sold in increasing numbers. Such automatic microscope systems may, depending on type and application software, be used for analysis of for example blood smears, tissue samples and body fluid samples. Automatic microscope systems have to be able to position the object, often a sample placed on a glass slide, in three dimensions relative to the optical subssystem of the microscope. In addition, the DM96 and DM1200 systems from CellaVision AB can fetch individual slides from specific positions in a cassette, analyse each slide individually and then restore each slide to a specific position.

In EP2204686A1 an analyser, i.e. an automatic microscope system, similar to the DM1200 from CellaVision AB is described The analyser in EP2204686 Al can position a slide in three dimensions (x, y and z) and it is capable of fetching/restoring slides from/to any position within a geometrical space using a handling device that can grip the slides. However, the analyser described in EP2204686A1 is designed with four main components, being the x, y and z mechanisms and the handling device, operating in cascade, meaning that each component will have to hold and position the whole mass of the components that follow. In order to achieve stable movements, the masses and the required forces grow by each component from the last to the first. Therefore microscope systems that operate in cascade often become large and heavy and still risk becoming slow and/or vibration sensitive. In addition, the handling device of the analyser in EP 2204686A1 requires an actuator of its own, summing up to at least four actuators for positioning and object handling. Efforts to design smaller, less cascade operating, lower moving mass microscope systems have been made. In WO2005119329A1 a flexure arrangement for x and z (vertical, focus) movements is disclosed. The x and z movements of the flexure arrangement are not wholly in cascade, but the arrangement is to be combined with a separate cascading y mechanism. The flexure arrangement extends in the z direction and may be vibration sensitive. The flexure arrangement can achieve a gear ratio larger than one in the z direction, meaning that the actuator used for z movement will move a longer distance than the resulting movement along the z direction.

In WO2008048150A1 an arrangement for x and z movements, with a low extension in the z direction, is disclosed. The x and z movements of WO2008048150A1 are not wholly in cascade, but the arrangement is to be combined with a separate cascading y mechanism. The arrangement can achieve a gear ratio larger than one along the z direction.

In JP2000098257A an arrangement for three dimensional positioning of a microscope stage using six linear actuators ("drive links"), six movable links and twelve ball joints is disclosed. The arrangement is not wholly in cascade. According to the abstract it uses at least three actuators but all figures show at least six actuators, which according to Fig. 1 and 4 of the published patent application work in pairs. According to all figures, the arrangement extends in the z (vertical) direction and may be vibration sensitive especially if there is play in some of the actuators or the ball joints. In neither of WO2005119329A1, WO2008048150A1 nor JP2000098257A, object handling is part of the concept. Object handling will add mass and actuators to these concepts.

Summary of Invention It is an object of the present invention to enable improvements in automated microscope technology in some or all the areas of: cost, size, cascade operation, mass, speed and sensitivity to outer vibration.

It is a further object of the present invention to enable robust object handling without any extra actuators.

More specifically the invention relates to a combination of an object holder and an

arrangement for positioning of the object holder along one, two or three directions. The object holder comprises contact elements that are pairwise compatible with press elements of the arrangement. The press elements are connected to two or three actuators of the arrangement. The lengths of the actuators can be adjusted along a first direction and the object holder can at least be translated along the first direction by the arrangement. In addition, the contact elements of the object holder can have flexible connections with an object space of the object holder. Similarly, the press elements of the arrangement can have flexible connections with the actuators. Depending on the use of such flexible connections, the object holder can also be tilted and/or rotated by the arrangement, making it possible to position parts of an object holder along a second and/or a third direction.

The main advantages of the combination of an object holder and a positioning arrangement according to the present invention are simplicity of design, small size especially along the third (z, vertical, focus) direction, low mass, possibly no cascade operation and few parts. Simplicity can be beneficial for cost, speed, reliability and serviceability. Small size and low mass can make transports during delivery and service easier and can be extra useful for small laboratories in the outskirts of infra-structure, at a space station or in outer space. Low mass can also make the microscope less sensitive to vibrations from outside. No cascading mechanisms can improve speed and few parts can cut costs.

The pairwise compatible press and contact elements can be designed to have quite large so called centering patterns, which together with the flexible connections can make the combination robust to manufacturing tolerances, and, in addition, to variations in relative positions of object holder and positioning arrangement when automatically handling object holders. Thereby the arrangement can also be used for automatic handling of object holders, like for example lifting an object holder from a nearby support or dropping an object holder in a nearby drop region. The lifting can be made with a predictable resulting position of the object holder along the third (z, vertical, focus) direction, which is an advantage from a focusing point of view. The handling of object holders can be achieved without any extra actuator, which is an additional advantage.

Brief Description of Drawings

The present invention will now be described by way of embodiments and with reference to the accompanying drawings, in which

Figure 1 shows some basic parts, some of them simplified, of a positioning arrangement. No object holder is shown;

Figure 2 shows some basic parts of an object holder. No positioning arrangement is shown; Figure 3 shows a combination of an object holder according to Fig. 2 and a positioning arrangement according to Fig. 1;

Figure 4 shows five different pairs of press elements and contact elements together with corresponding centering patterns;

Figure 5 shows two different types of flexible connections that can be used as parts of a positioning arrangement according to the invention,

Figure 6 shows three different types of flexible connections that can be used as parts of an object holder according to the invention;

Figure 7 shows three different examples of actuators in a positioning arrangement;

Figure 8 shows a two dimensional view of a combination of an object holder and a positioning arrangement while focusing is performed;

Figure 9 shows some additional details of a positioning arrangement holding an object holder;

Description of Embodiments The invention is described more fully hereinafter with reference to the accompanying drawings, in which examples of embodiments of the invention are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the specific embodiments set forth herein. It should also be noted that these embodiments are not mutually exclusive. Thus, components or features from one embodiment may be assumed to be present or used in another embodiment, where such inclusion is suitable.

Fig. 1 shows a platform 100 in the form of a sheet with a rectangular perimeter, two actuators and three press elements 121, 122 and 123. The first actuator comprises a linear stepper motor 102 that can position a sledge 104 that can glide on two seek shafts 106 and 108 along a first direction (the x direction).

The second actuator comprises another linear stepper motor 112 that can position another sledge 1 14 that can also glide on the two seek shafts 106 and 108 along the first direction. Each actuator can be connected to the platform 100 through at least one actuator connection. In this example each actuator is connected to the platform 100 both via its linear stepper motor and through the shared seek shafts 106 and 108. A first press element 121 is connected with the first actuator using a first connection 131 to the sledge 104, a second press element 122 is connected with the second actuator using a second connection 132 to the sledge 114 and a third press element 123 is connected with the first actuator using a third connection 133 to the sledge 104. In Fig. 1, the press elements 121, 122 and 123 are represented by black spheres and the connections 131, 132 and 133 are represented by dashed lines.

The actuators can have adjustable lengths along the first direction. In the example in Fig.1, the length along the first direction of the first actuator is adjusted by moving the sledge 104 using the linear stepper motor 102 and the length of the second actuator is adjusted by moving the sledge 114 using the linear stepper motor 112. Although the first and second actuators in Fig.1 share seek shafts 106 and 108, the sledges 104 and 114 can still be positioned independently of each other. The sharing of seek shafts can reduce the number of parts and save weight, space and production costs.

The press elements have intended, nominal, relative displacements along a second direction (the y direction), which is perpendicular to the first direction (the x direction). The second press element 122 has a first displacement relative to the first press element 121 along the second direction. Similarly, the third press element 123 has a second displacement relative to the first press element 121 along the second direction.

Fig. 2 shows an object holder 200 with three contact elements 221, 222 and 223. The object holder can have a designated object space, which is not pointed out in Fig. 2. The contact elements 221 , 222 and 223 are connected with the object space using fourth to sixth connections respectively. The fourth to sixth connections (not pointed out in Fig. 2) can be rigid but flexible designs can also be used, as exemplified below.

The contact elements have intended, nominal, relative displacements along a fourth direction, which can correspond to the y direction when the object holder is held by the positioning arrangement. The second contact element 222 has a third displacement relative to the first contact element 221 along the fourth direction. Similarly, the third contact element 223 has a fourth displacement relative to the first contact element 221 along the fourth direction.

The object holder 200 can have multiple sets of contact elements, where each set comprises a first, a second and a third contact element with properties according to above and where the sets are displaced with respect to each other along the fourth direction. The third and fourth displacements may however differ between sets due to, for example, manufacturing tolerances. Fig. 3 shows a combination of an object holder 200 according to Fig. 2 and a positioning arrangement according to Fig. 1, where the object holder is held by the positioning

arrangement.

By closing the gap between the sledges 104 and 114 under the influence of the linear stepper motors 102 or 112, it is possible for the positioning arrangement to apply press from two essentially opposite directions on the object holder 200. The object holder can be held by the positioning arrangement, assuming, among other things, that there is a nominal fit between the first and third displacements as well as a nominal fit between the second and fourth

displacements, for at least one set of contact elements of the object holder 200.

However, there are some features of the combination of positioning arrangement and object holder that facilitate robust operation of positioning arrangements and object holders even without this nominal fit. A first advantageous feature is that each pair of press element and contact element can have a centering pattern that makes is possible to center the press element relative to the contact element under press, provided that the initial contact is made within the centering pattern.

Referring to Fig. 1 and Fig. 2 again, for practical reasons the first press element 121 will have to fit the first contact element 221, the second press element 122 will have to fit the second contact element 222 and so on. However, the first press element 121 does not necessarily have to fit any other element than the first contact element 221 while the first press element 121 may fit for example the second press element 122. Press/contact element is thus not necessarily equivalent to some kind of male/female elements.

In Fig. 4 five compatible pairs of press and contact elements are shown. In Fig. 4A a rotationally symmetrical rod 400 with a spherically shaped right end is shown together with a cylindrical hole 402 bored with a drill having a conical tip. The corresponding centering pattern is a circle 404 with the same shape and dimensions as the hole 402, meaning that if the spherical end of the rod 400 is pressed to the hole 402, centering is possible as long as the center of the rod is within the centering pattern 404 (the hole). In Fig. 4B a rod 410 with a conical end is combined with a hole 412 like in Fig. 4A. The centering pattern is still a circle 414 with the same shape and dimensions as the hole 412. In Fig. 4C a rod 420 with a square cross section and a pyramidical right end is shown together with a (theoretical) square hole 422. The centering pattern 424 has the same shape and dimensions as the square hole 422. In Fig. 4D a sheet 430 with unknown prolongation in the y direction (i.e. into and out from the plane of the figure) and with a rounded right end is shown together with a slot 432 (possibly milled). The centering pattern 434 has a height corresponding to the height of the slot 432, while the width is limited by the limitations of the sheet 430 and the slot 432 in the y direction. Fig. 4E differs from Fig. 4D by the right end of the sheet 440 being sharp instead of being rounded. The slot 442 and the centering pattern 444 correspond to slot 432 and centering pattern 434.

It is possible to integrate the first and third press elements into one integrated press element. Similarly, it is possible to integrate the first and third contact elements into one integrated contact element. An integrated press element and an integrated contact element can be designed according to Fig.4D. If the centering pattern of an integrated press or contact element is wide along the second direction, the corresponding displacements can then be set to, for example, intervals of possible displacement values.

The pairs of Fig. 4 will have different movement properties once they have been pressed together. The pair in Fig. 4A will, when surfaces are perfect, have contact along a circle.

Furthermore, it will be possible to keep the spherically shaped end in contact with the hole 402 and still move the other end of the rod 400 in two dimensions in the y-z plane. Such a pair will be referred to as having a "two dimensional movement property".

The pair in Fig. 4D will, when surfaces are perfect, have contact along two lines. It will be possible to keep the rounded end of the sheet 430 in contact with the slot 432 and still move the other end of the sheet 430 in the z direction. Such a pair will be referred to as having a "one dimensional movement property". A pair with "at least a one dimensional movement property" has a one dimensional or a two dimensional movement property.

It can be possible to combine the rod 400 with the spherical end of Fig.4A with the slot 432 of Fig. 4D. The sphere/slot pair will have a centering pattern like in Fig. 4D and it will also allow for two-dimensional movement of the other end of the rod 400. However, the sphere/slot pair will, when surfaces are perfect, have contact at only two points instead of along two lines. These movement properties is a second advantageous feature when it comes to robust operation of positioning arrangements and object holders, since they facilitate tilt and/or rotation of the object holder. The other three pairs of Fig. 4 will not allow for similar movements without altering the relative position of the press element relative to the contact element along the x direction.

Displacement of two elements along a direction can be defined as the distance along the direction between the center (along the direction) of one of the two elements and the center of the other element. The center can be determined as a center of a centering pattern, if applicable. In order for a positioning arrangement and an object holder to work successfully together it is not sufficient that the press and contact elements are compatible pairs and have appropriate displacements and centering patterns, the attitudes in three dimensions of the press and contact elements must also be compatible. The expression "press direction" will be used to describe a center direction along which a press element can apply force. "Press direction" will also be used to describe a center direction along which a contact element can receive force. In Fig. 4A the "press direction" is along the line 401 and with a direction from the press element to the contact element. Observe that either one of 400 and 402 can, depending on which one is used in the positioning arrangement and in the object holder, be the press element. Although press direction is defined as a center direction, it can still be possible to apply and receive forces that are directed with some angle with respect to the press direction. Similarly, the press directions in Fig.4B to Fig. 4E are along the lines 411, 421, 431 and 441 , respectively. In Figure 1 , first and third press elements 121 and 123 can, depending on their details, have a first press direction that is essentially identical to the negative x direction, while the second press element 122 can have a second press direction that is essentially indentical to the positive x direction and essentially opposite to the first press direction. In Figure 2, first and third contact elements 221 and 223 can have a third press direction and the second contact element 222 can have a fourth press direction which is essentially opposite to the third press direction. Without reference to the coordinate system of the positioning arrangement it is not possible to describe the relation of the third press direction to the first press direction or the fourth press direction to the second press direction, i.e. it is not possible to determine whether an isolated object holder 200 of Fig.2 is oriented to fit the positioning arrangement of Fig. 1 or not.

A third advantageous feature for robust operation is that the positioning arrangement and/or the object holder can have flexible connections allowing for individual pairs of press and contact elements to deviate some along, for example, the second (y) direction from their corresponding displacements during operation. In Fig.5 A an example of a flexible connection 533 is shown together with a sledge 504 and a press element 523. The flexible connection 533 has a thin waist 535 making it possible to easily bend the left end of the connection 533 around a vertical axis through the waist 535. Thereby the press element 523 can deviate some from its nominal position along the y direction of the figure at the cost of a limited change of extension along the x direction of the figure. A flexible connection 533 according to Fig. 5 A can be useful as an alternative to connection 133 in Fig. 1 and then allow for the press element 123 to deviate some along the y direction compared to its nominal displacement. In Fig. 5B another example of a flexible connection comprising parts 516, 518 and 520 is shown The block 516 is mounted using two thin sheets 518 and 520 on a sledge 514. The sheets 518 and 520 allow the block 516 to move along the x direction of the figure at a limited change of height along the z direction of the figure. The change in the z direction can be used for refocusing purposes. The sheets 518 and 520 are, like for so called "flexures" in general, quite resistant to movements of the block 516 along, in this case, the y direction, and to rotations of the block 516. A flexible connection according to Fig.5B can be useful as an alternative to connection 132 in Fig.1 and allow for the press element 122 (not shown in Fig.5B) to move a little along the z direction. In case the flexure of Fig.5B is designed to be a little less resistant to rotation around the z direction of the figure, it can be used both for easy movement of a press element along the x direction and for limited movement in the y direction by rotation. The flexible connection according to Fig. 5B can also be used in another way, when appropriately oriented, for achieving flexibility in the second (y) direction by being used as an alternative to connection 133 of Fig.1. It can be used as a second flexure level in a replacement for connection 132. The flexible connections can also be useful for three dimensional positioning of the object holder 200 as will be described later.

In Fig.6 some examples of how object holders can be designed with flexible connections are shown. In Fig.6A the object holder 600 is shown from a view corresponding to from the right in Fig. 2. The waist 602 allows for the tap 604 to be easily bent in the y direction of the figure and thus the contact element 223 is allowed to move along the y direction with a limited change of height along the z direction. Contact element 221 is shown for reference. In Fig.6B the object holder 610 is shown from a view corresponding to from the front in Fig. 2. The waist 612 allows for the tap 614 to be easily bent in the x direction of the figure and thus the contact element 222 is allowed to move along the x direction with a limited change of height along the z direction. The change in the z direction can be used for refocusing purposes. Contact element 223 is shown for reference.

In Fig.6C the object holder 620 is shown from a view corresponding to from above in Fig. 2. The waist 622 allows for the tap 624 to be easily bent in the y direction of the figure and thus the contact element 223 is allowed to move along the y direction with a limited change of extension along the x direction. The waist 632 allows for the tap 634 to be easily bent in the y direction of the figure and thus the contact element 222 is allowed to move along the y direction with a limited change of extension along the x direction. Embodiments according to 6B and 6C may be combined in order to make, for example, the contact element 222 flexible along both the x and y directions. Contact element 221 is shown for reference.

Fig. 7A shows an example of a three dimensional positioning arrangement where a third actuator is implemented as a differential actuator 710 in cascade with sledge 104 of the first actuator, which was shown in Fig.1. The third connection 733 is now designed for connecting the differential actuator 710 with the third press element 123. The length of the third actuator can be adjusted along the first direction as a sum (with signs) of a movement of the sledge 104 using the linear stepper motor 102 and of an adjustment of the length of the differential actuator 710. Fig. 7B shows another example of a three dimensional positioning arrangement where the third actuator is implemented using a separate sledge 708 and a separate linear stepper motor 706. The length of this third actuator can be adjusted along the first direction by moving the sledge 708 using the linear stepper motor 706. The first actuator is now

implemented using a sledge 704 and a linear stepper motor 102. Fig. 7C shows yet another example of a three dimensional positioning arrangement where the third actuator is implemented like in Fig. 7B while the first actuator is implemented using a linear stepper motor 712 and a first connection 731 which can be kept from rotating by parts inside the linear stepper motor 712. Fig. 7B and 7C show sledges 704 and 708 that each glide on a single seek shaft but that is only in order to simplify the Figures. The sledges 704 and 708 can, for example, be asymmetrically designed to overlap along the y direction and thus still share the seek shafts 106 and 108. Although the use of three independent actuators, like in Fig. 7B and Fig. 7C, make the corresponding positioning arrangement free from cascade, the requirements on real time synchronisation of stepper motor movements become tougher in order to avoid unintentional differential movements of first and third press elements 121 and 123. The actuators of Fig. 7 all have adjustable lengths along the first direction (the x direction). Each actuator of Fig. 7 can be connected to the platform 100 through at least one actuator connection. The first and second displacements can be defined for press elements 121, 122 and 123 just like in connection with Fig. l . Parts l l2, 114, 131, 132 and 133 of Fig.7 are the same as in Fig.1 and are shown for reference.

In order to get the object holder 200 to being firmly held by the positioning arrangement like shown in Fig.3, the object holder 200 can be put there by a user or be lifted there from a nearby position by the positioning arrangement itself. Assuming that the object holder 200 is resting on some support with the first to third contact elements 221 , 222 and 223 being close enough to their corresponding first to third press elements 121, 122 and 123, the press element 122 can, for example, begin to move towards press elements 121 and 123. At some point of time a first one of the three pairs of press and contact elements will get into contact. As a result of the contact, the press and contact elements will begin to interact using forces essentially along, and opposite to, the press direction. Depending on friction forces between the object holder 200 and its rest, the object holder may move along with a moving press element for a while. As the press elements continue to move towards each other, other pairs of press and contact elements will also get into contact. At some point in time, the object holder can no longer escape the press elements and, if it has not happened already, each pair of press and contact elements will begin to center. During centering the object holder may move relative to its support and any flexible connections within the positioning arrangement and/or within the object holder can begin to flex The press and contact elements can move even closer to each other and as a possibly last event the press forces become strong enough to lift the object holder from its support.

A successful lifting of the object holder will not depend only on the relative positions at the beginning of the lift and the centering patterns of the individual press/contact element pairs, but also on the possible ranges and forces of the flexible connections as well as on how much the displacements of the positioning arrangement differ from their corresponding

displacements of the object holder. When all three pairs of press and contact elements have centered and have been pressed together to full contact, the movement of press element 122 relative to press elements 121 and 123 can continue provided that there is flexibility along the first (x) direction, for example in connection 132. Depending on design, such a continued movement can, like described in connection with Fig.5B, lead to an adjustment of the position of press element 122 along the third (z) direction, i.e. to a focus adjustment.

In Fig.8 an example of a focus adjustment is shown. In Fig.8A the object holder 200 is held between sledges 104 and 114 using connections 131 (not shown), 132 and 133 and three pairs of press and contact elements, out of which only press element 122 has a reference sign in Fig.8. In Fig. 8B the sledge 114 has been moved slightly towards sledge 104 using the linear stepper motor 112. Since the connection 132, in this example, is flexible along the first (x) direction with a resulting change of height along the third (z) direction, press element 122 and contact element 222 (not referenced) are lowered compared to in Fig.8 A. As a result, and since connections 131 (not shown) and 133, in this example, are not flexible along the first (x) direction, the object holder 200 is now tilted a little to the left but kept at essentially the same position along the first (x) direction. Due to the flexed state of connection 132 in Fig.8B, press forces are now acting on both sides of the object holder 200. Such press forces facilitate a firm holding of the object holder, which in turn makes reliable coordinated moves along the first (x) direction and further focusing adjustments possible. Linear stepper motor 102 is shown for reference.

The example positioning arrangements and object holders in Fig.1, Fig.7 and Fig. 8 each use three discrete pairs of press and contact elements for their operation. Each pair of press and contact elements is surrounded by two connections; one of the first to third connections belonging to the positioning arrangement and one of the fourth to sixth connections belonging to the object holder. Depending on which of the first to sixth connections that are flexible or not, a pair of press and contact elements can be surrounded by zero, one or two flexible connections. In addition, the flexible connection/s, if any, can, depending on design, be flexible along different directions.

One possible design for achieving stability and well defined positions of a firmly held object holder is to let one pair (denoted "A" below) have zero flexible connections, to let another pair ( "B") have one or two flexible connections that are flexible (essentially) along the second (y) direction only and to let the final pair ("C") have one or two flexible connections that together are flexible in both the first (x) and second (y) directions with resulting movements in the z direction. Then "A ", which is a pair without flexibility, will have a fix position that is defined by the position of its corresponding actuator only. Further, "B" will be positioned at an intersection, in three dimensions, of {where the contact element of "B" can be situated, including flex, when the contact element of "A" is fixed} and {how the press element of "B" is allowed to flex in the second direction with respect to the position of its corresponding actuator}. Pair "C" will be positioned at another intersection, also in three dimensions, of { where the contact element of "C" can be situated when the contact elements of "A" is fixed and "B" is at its intersection} and {how the press element of "C" is allowed to flex with respect to the position of its corresponding actuator} . If more flexibility than in the possible design mentioned above is allowed, the positions of the pairs "A", "B" and "C" may no longer be uniquely dependent on the positions of the actuators and there may also be (additional) problems with sensitivity to outer vibrations and/or with oscillations after intended

movements.

The possible design with "A", "B" and "C" mentioned above can also, provided that there are three actuators like in Fig.7, be used for achieving limited movements of at least parts of the object holder 200 in the y direction. By moving pair "B" to, for example, the left using its corresponding actuator, the object holder 200 will be rotated around an axis, essentially parallel to the third (z) direction, through "A". The flexible connection/s of "B" will allow "B" to move by rotation in the second (y) direction and thus keep the pair "B" in centered and in full contact. The rotation will also cause "C" to move both in the first (x) and the second (y) directions, which will be allowed by the flexible connection/s of "C" at limited change of height of "C" along the third (z) direction. The actuators can be adjusted in order to compensate for the, possibly, unwanted changes along the first (x) and third (z) directions. By using geometrical properties of the positioning arrangement and the object holder and mathematical expressions corresponding to the described intersections, a positioning algorithm that computes appropriate simultaneous changes of all three actuators can be developed. For the possible "ABC" design described above, the y and z movements of a particular point within the object holder will depend on the position of the point within the object holder. The reasons are, naturally, that the z movements (focus adjustments) are performed using tilt of the object holder and that the y movements are performed using rotation of the object holder The resulting z and y movements for a particular point will depend on geometrical leverage as well as on the angles of tilt and rotation. Since the z movements of the object holder will depend e.g. on the position within the object holder, a gear ratio of a combination of a positioning arrangement and an object holder is preferably computed at a well defined state, for example using zero intended position change in the y direction and with the particular point being the pair of press and contact elements where the intended change along the z direction occurs. The gear ratio can be computed as the movement along the first (x) direction per movement along the third (z) direction. A gear ratio larger than one thus indicates that the movement along the first direction is reduced in magnitude in the resulting third (z) direction. When a combination of positioning arrangement and object holder according to the invention is designed, it can be advantageous to design it with the geometrical leverage for y and z movements in mind. The stability of the combination of positioning arrangement and object holder can depend on how "A", "B" and "C" are placed along the second direction during design, i.e. on the first and second displacements.

When the positioning arrangement is moving an object holder along the first (x) direction in a start-stop-start-stop fashion, the mass of the object holder has to be accelerated and deaccelerated accordingly Depending on the design of the flexible connections that provide the third direction (z, vertical, focus) adjustments, the object holder may come to rest quicker after a movement when the movement is performed in one direction compared to in the opposite direction.

As pointed out above, a pair of press and contact elements can be surrounded by zero, one or two flexible connections. The number of flexible connections can, within limits, be quite easily modified by a user depending on the choice of type of object holder to use.

As a continued example, now referring to Fig.1 and Fig.2 and assuming that "C" is the pair of press element 122 and contact element 222, connection 132, which belongs to the positioning arrangement, can be designed to be quite stiff and to give a high gear ratio. In addition, a user can choose between one object holder with a rigid connection for contact element 222 and one object holder with a connection for contact element 222 that is softer than the one of connection 132 and with a lower gear ratio than the gear ratio of connection 132. If the object holder with the rigid connection is used, the gear ratio of connection 132 will determine how much press element 122 and contact element 222 will move in the third (z) direction per relative movement of sledge 114 in the first (x) direction. If instead the object holder with the soft connection is used, its soft connection will flex a longer distance than the stiff er connection 132. The reason is that the two flexible connections work in series and with the same pressing force. Thereby the resulting gear ratio of the series will be closer to the gear ratio of the soft connection in the object holder than to the gear ratio of connection 132. By using object holders with rigid connections for the contact element 222 for samples that essentially are a monolayer, it is possible to achieve a high gear ratio within a narrow focus interval. By using object holders with soft flexible connections for the contact element 222 for thicker samples it is possible to get a lower gear ratio but a greater focus interval using the same positioning arrangement.

In a similar way, an object holder with a rigid connection in its y direction for, for example, contact element 222 can be used if the analysis will not use y movements performed by the positioning arrangement. Then a connection 132 which is quite stiff (not so flexible) in the y dimension can be just enough for coping with production tolerances and give high stability and speed to the analysis due to the stiffness.

If instead the analysis will use y movements performed by the positioning arrangement, a type of object holder with a flexible connection for contact element 222 being softer in its y direction than the connection 132 can facilitate larger y movements at reasonable force levels, perhaps at the price of a lower analysis speed.

Referring to Fig.9 with a two dimensional view of a positioning arrangement holding an object holder 200, some possible modes of a positioning arrangement according to the present invention will be described in more detail. By moving the sledges 104 and 1 14 using the linear stepper motors 102 and 1 12, the object holder 200 can be firmly held and transported along the first (x) direction. If a positioning arrangement is implemented using first to third connections that all are rigid along the first (x) direction and intended for holding a object holder 200 that is also rigid in its x direction, it can be advised to limit the pressing forces for example by limiting the currents of the linear stepper motors 102 and 112.

An analysis mode is shown if Fig. 9 with the object holder 200 being situated, along the first (x) direction, where it is possible to perform analysis of some object space (not specified in Fig.9) of the object holder 200 using the illumination source 902, the optical subsystem 904 and the electronic image sensor 906. An optical axis 908 of the optical subsystem 904 is indicated by a dashed line. The object space can be searched along the first (x) direction and focus adjustments can be made as pointed out in connection with Fig.8. During analysis, it may be desired to switch to using a different set of contact elements. Such a shift can be made by dropping the object holder 200 on to the support platform 920, followed by a translation of the object holder 200 to the next desired set of contact elements along the second (y) direction and finally by lifting the object holder again, now using the new set of contact elements. The translation of the object holder along the second (y) direction can be performed by some separate actuator or by a sledge using some link mechnism at some certain position of the sledge. The support platform 920 can be designed to support the object holder 200 when not held by the positioning arrangement, to let the illumination from the illumination source 902 through and optionally, to let sledges 104 and 114 move underneath it.

When the analysis of the object of the current object holder has been completed the object holder can be transported along the first (x) direction to a drop region 914 where it can be dropped between the seek shafts simply by moving sledges 104 and 114 apart from each other. In a design where there is no room in the first (x) direction for a separate drop region, it is possible to use an alternative drop region 916 located for example beneath the illumination source 902. If so, the object holder can be dropped on to the support platform 920 and then the illumination source 902 and the support platform 920 can be moved out of the way via an illumination release mechanism 922 by use of sledge 104.

When the next object holder is due for its analysis it may be situated at the top of a stack 900. The rest of the stack 900 may be accessible for a user during analysis. Thereby a user may, for example, rearrange the order of the stacked object holders. The stack 900 can be spring loaded from underneath. In order to release the next object holder for analysis, a stack release mechanism 924, can be activated by the sledge 114 by going far to the left in the first (x) direction. The goal of the release can be to put the next object holder on top of the support platform 920, which may be involved in the release of the next object holder. In connection with releasing the next object holder, a barcode of the next object holder can be identified by a barcode reader placed in or nearby a barcode region 910 A barcode can also be identified in some other way, for example by using the optical subsystem 904. The object holder 200 can now be lifted from the support platform 920 and can then be transported to the oil drop region 912, which can also act as an alternative barcode region, before or during the next analysis. The use of long seek shafts facilitates a greater number of regions along the first (x) direction. However, for long seek shafts it is preferrable to increase the diameter of the shafts in order to keep deformations and sensitivity to vibrations under control.

The positioning arrangement may be operated using other modes, using other geometrical designs and/or using other actuators than the ones described here. Some of the movements may be performed in other directions that in the first (x) direction. For example, object holders may be transported along the second (y) direction before and/or after an analysis. The use of a stack, a barcode region, an oil drop region and/or a drop region may not be necessary.

The sledges can be used for other operations than the ones described here. However, when sledges are used for positioning of the object holder during analysis, additional loads on the sledges may cause elastic deformations of the positioning arrangement and affect its accuracy. In addition, sledges may not be used at all. If so, other moving parts of the actuators may be used for achieving some of the operations described above.

For description purposes a platform 100 in the form of a sheet of material has served as a reference plane for other components. Although the platform 100 is not necessarily

implemented as a separate physical sheet of material in a microscope system design, it can still exist as a virtual reference plane.

The actuators described mainly with reference to Fig.1 and Fig.7 are examples of possible actuators.

Sledges on seek shafts are the dominant design within disk player technology since the CD player age and represent a well-known, well-described, mature technology with low production costs. In US5926451 it is described how a sledge based actuator can be designed and how clearance around seek shafts can be reduced using a "pressing portion" according to that invention The claims of that patent are limited to optical disk units. A sledge gliding along two seek shafts in the presence of "pressing portions", one per seek shaft, can be a low friction actuator solution where zero play is possible. It is not necessary to use linear stepper motors for the actuators according to the present invention. However, the cost reduced motor mechanisms of disk players are intended as coarse positioning meachanisms. In a disk player, another system, often based on a voice coil, is performing the fine positioning using a high frequency control loop. However, other actuator designs, that can move the actuator ends of the first to third connections in predictable ways essentially along the first (x) direction, are possible to use. In Fig.7, the use of a linear stepper motor 712 and a first connection 731 which can be kept from rotating by parts inside the stepper motor 712 is limited to Fig.7C. That actuator is preferrably used together with a connection 731 that is not flexible, since even a small rotation of connection 731 around its own axis would cause an unwanted disturbance if connection 731 is flexible.

The object holder design can be as simple as a rectangular glass slide of the type common in microscopy, but where at least parts of two parallel edges have been rounded to circular shape and now have the function of contact elements like in Fig.4D. The corresponding press elements in the positioning arrangement can then be slots, like in Fig.4D, for holding directly around the rounded edges of the glass slide. The height of the slots will limit the centering patterns. The object space can be any part of the glass slide. The fourth to sixth connections between the contact elements and the object space are due to the simple design also of glass and rigid.

Another possible type of object holder design can be as simple as a rectangular glass slide of the type common in microscopy, but where two parallel edges have been given at least one set of contact elements in the form of drilled holes of the type in Fig.4A . The diameters of the drilled holes will limit the centering patterns. The object space can be any part of the glass slide The fourth to sixth connections between the contact elements and the object space are due to the simple design also of glass and rigid.

In theory, three prefabricated contact elements may be fastened on a rectangular glass slide of the type common in microscopy by a user, but there can be quality issues The displacements of the contact elements could be out of tolerance and/or the fastening of the contact elements could become flexible connections with unwanted properties. The object space can be any part of the glass slide.

In another design, the object holder can consist of one or more prefabricated parts, including all contact elements and connections, and a glass slide, that can be integrated during manufacturing or attached to the prefabricated part/s by a user, possibly after a sample has been attached to the glass slide. Possibly, the glass slide is attached to the prefabricated part/s via adhesive tape or glue. The adhesive tape can be of a type that facilitates reuse of the prefabricated part/s in case this can be allowed from an analysis quality point of view. Another possibility is that the glass slide is held firmly by the prefabricated parts without adhesive tape or glue, for example by being pushed into specially designed slots by a user or by being placed between two or more prefabricated parts that are then snapped together.

In order to get the sample side of the glass slide on a predictable height in the positioning arrangement, the prefabricated part/s can be produced with a certain glass thickness in mind. Alternatively, the prefabricated part/s can be designed to align the sample side of the glass slide with a certain level within the prefabricated parts, for a reasonable interval of possible thicknesses of the glass slide.

The slides mentioned above can be made of other materials than glass, as long as the optical, chemical, mechanical and other properties of the slide are fulfilling the requirements of the type of analysis to be performed. The slides mentioned above do not have to be rectangular either.

An object space can be defined as a space within a object holder where a sample can be attached. The attachment can be made to a surface that has been integrated with the object holder during production. The attachment can be made to a surface that is integrated with the object holder after production or integrated even after the sample has been attached to the surface. A sample that is attached in an object space is most often to be analysed with an optical subsystem having an optical axis along a particular direction of the object space. A normal direction of an object space can be defined as a that particular direction.

There is a possibility for a designer or a even for a user to choose the material of the contact elements with respect to the material of the corresponding press elements in order to control where wear is most likely to occur.

A y mechanism can be included in a object holder for positioning the slide in the y direction relative to the object holder during analysis.

In Fig.3, the object holder 200 is of a rectangular shape with the longest sides directed along the second (y) direction. Such a design may facilitate short seek shafts. However, the longest sides, if there are significantly longer sides, could also be directed along the first (x) direction. The latter design may facilitate more clearing for dropping object holders between the seek shafts. The latter design may also facilitate better geometrical leverage for the rotation and tilt movements leading to y and z movements respectively. The latter design may complicate the design of the rigid parts of an object holder, since the pressing forces pass through the object holder along longer paths compared to in the former design. It is possible that some regions of an object holder, due to geometrical leverage considerations, are not useful for three dimensional analysis. Such regions may be used for labels or other objects that have more relaxed requirements on y and/or z movements.

A positioning arrangement according to the present invention can be the main mechanical system of a small stand alone microscope or it can be just one of many similar modules inside a large automated microscope system. A positioning arrangement according to the present invention can, depending on design, be limited to use for translation of an object holder in only one dimension (x), in two dimensions (x and limited z) or in three dimensions (x, limited y and limited y). The limited range of the arrangment according to the present invention in the y direction can be overcome by using an outer (cascade) y mechanism (possibly slower or not so accurate/repeatable) that can be used together with the arrangement according to the invention for, for example, searching for monolayers in the y direction, stepping between rows when scanning a sample row wise and even for a large movement of the whole arrangement to another objective/system position. The limited range can also be overcome by translation of the object holder in the y direction between different sets of contact elements, as has been described in connection with Fig.9. A similar way of overcoming the limited range can be used if all pairs of press and contact elements allow for translation along the y direction, like for exemple for the pairs of Fig.4D and Fig.4E. Such a design of object holder and positioning arrangement can be regarded as having an infinite number of subsets of contact elements. It can be used like an object holder with a number of sets of contact elements, which was described in connection with Fig.9.

Oil immersion objectives are designed to be used with immersion oil between the objective and the sample. When an analysis using immersion oil is to be finished, lowering of the sample/object holder a couple of millimeters while still being located at the optical subsystem 904 can be advantageous for minimising oil spillage in the positioning arrangement. The object handling capabilities of the combination of positioning arrangement and object holder according to the present invention makes it possible to instead simply drop the object holder, perhaps onto a support 920 before transporting it to a drop region 914 or 916.

The object handling properties described above combined with an object holder that possibly keeps the sample on a predictable height in the positioning arrangement, makes it possible to operate the positioning arrangement succesfully using a quite small focus interval. A position within the object holder having a geometrical leverage of 20 mm will have a ±50 μιη focus interval for only a ±0.25% tilt of the object holder.

A traditional positioning arrangement without such object handling capabilities may instead have to be equipped with a z mechanism with a much wider focus interval.

Although the press elements have been described to move towards each other when applying pressure on or lifting the object holder, it is still possible to grip, using a differently designed positioning arrangement, from inside a differently designed object holder and move the press elements from each other when applying pressure on or lifting the object holder.

As pointed out above, the object holder 200 can have multiple sets of contact elements, where each set comprises a first, a second and a third contact element. In addition, some of these contact elements can be integrated. Such multiple sets of contact elements, can, as pointed out above, be used for holding the object holder at a number of different positions along the second (y) direction. However, it is also possible to design a positioning arrangement with mulitple sets of press elements or to combine mulitple sets of press elements with multiple sets of contact elements.

By using different types of object holders, the same positioning arrangement can handle slides of different sizes, especially since the positioning arrangement is not necessarily limited to holding object holders of any certain length along the first (x) direction.

The positioning arrangement can be controlled by control circuitry configured for controlling the actuators of the positioning arrangement. Such control circuitry can be configured for lifting, translating, tilting, rotating and other, movements of an object holder as has been described above.

It will be appreciated that the foregoing description and the accompanying drawings represent non-limiting examples of the methods and apparatus taught herein. As such, the invention is not limited to the specific embodiments provided in the foregoing description and

accompanying drawings, but is instead limited only by the following claims and their legal equivalents.

Claims

A microscope system comprising an arrangement for positioning of an object holder at least along a first direction characterised in the arrangement comprising

a first platform (100),

a first actuator (102, 104, 106, 108) having an adjustable first length along the first direction and having at least a first actuator connection to the first platform, a second actuator (1 12, 114, 106, 108) having an adjustable second length along the first direction and having at least a second actuator connection to the first platform, a first press element (121) having a first connection (131) to the first actuator, a second press element (122) having a second connection (132) to the second actuator and a third press element (123) having a third connection (133) to the first actuator, wherein the first (121) and third (123) press elements have an essentially common first press direction which is essentially parallel to the first direction,

the second press element (122) has a second press direction which is essentially opposite to the first press direction,

the second press element (122) has a first displacement relative to the first press element (121 ) along a second direction, which is perpendicular to the first direction, a third direction is perpendicular to the first and second directions and

the third press element (123) has a second displacement relative to the first press element (121) along the second direction.

An arrangement according to claim 1, wherein the first (121) and third (123) press elements are integrated to a common first and third press element.

a first platform (100),

a first actuator (102, 104, 106, 108; 102, 704, 106, 108; 712) having an adjustable first length along the first direction and having at least a first actuator connection to the first platform, a second actuator (112, 114, 106, 108) having an adjustable second length along the first direction and having at least a second actuator connection to the first platform, a third actuator (102, 104, 710, 106, 108; 706, 708, 106, 108) having an adjustable third length along the first direction and having at least a third actuator connection to the first platform,

a first press element (121) having a first connection (131 ;731) to the first actuator, a second press element (122) having a second connection (132) to the second actuator and

a third press element (123) having a third connection (733; 133) to the third actuator, wherein the first (121) and third (123) press elements have an essentially common first press direction which is essentially parallel to the first direction,

the second press element (122) has a first displacement relative to the first press element (121) along a second direction, which is perpendicular to the first direction, a third direction is perpendicular to the first and second directions and

4. A microscope system according to claim 1, 2 or 3, wherein the third direction is

essentially parallel to an optical axis (908) of the microscope system.

5. A microscope system according to claim 1 or 3, wherein each of the press elements ( 121, 122, 123) is designed to be compatible with at least one type of contact element resulting in a pair of press and contact elements that has a two dimensional movement property.

6. A microscope system according to claim 1 or 3, wherein each of the press elements ( 121, 122, 123) is designed to be compatible with at least one type of contact element resulting in a pair of press and contact elements that has at least a one dimensional movement property

7. A microscope system according to claim 1 or 3, wherein at least one of the first to third connections is flexible along at least one of the first and second directions.

8. A microscope system according to claim 1 or 3, wherein

the second connection (132) is flexible at least along the first direction at a

change of extension along the third direction.

9. A microscope system according to claim 1 or 3, wherein

the first connection (131 ; 731) is rigid,

the second connection (132) is flexible along the first direction at a limited change of extension along the third direction,

the second connection (132) is also flexible along the second direction and

the third connection (733; 133) is flexible along the second direction.

10 A microscope system according to claim 1 or 3, wherein the first displacement is

smaller than the second displacement.

11. An object holder (200; 600; 610; 620) for use in a positioning arrangement in a

microscope system characterised in the object holder comprising

an object space and

a first set of contact elements comprising a first (221), a second (222) and a third (223) contact element, wherein

the first contact element (221) has a fourth connection to the object space

the second contact element (222) has a fifth connection to the object space

the third contact element (223) has a sixth connection to the object space

the first (221 ) and third (223) contact elements have an essentially common third press direction,

the second contact element (222) has a fourth press direction which is essentially opposite to the third press direction,

the second contact element (222) has a third displacement relative to the first contact element (221) along a fourth direction, which is perpendicular to the third press direction,

a fifth direction is perpendicular to the third press direction and the fourth direction and the third contact element (223) has a fourth displacement relative to the first contact element along the fourth direction.

12. An object holder according to claim 11, wherein the first (221) and third (223) contact elements are integrated to a common first and third contact element.

13. An object holder according to claim 11 or 12, wherein a normal direction of the object space is essentially parallel to the fifth direction.

14. An object holder according to claim 11, wherein each of the contact elements (221, 222, 223) is designed to be compatible with at least one type of press element resulting in a pair of press and contact elements that has a two dimensional movement property.

15 An object holder according to claim 11 or 12, wherein each of the contact elements (221, 222, 223) is designed to be compatible with at least one type of press element resulting in a pair of press and contact elements that has at least a one dimensional movement property.

16. An object holder according to claim 11, wherein at least one of the fourth to sixth

connections is flexible along at least one of the third press direction and the fourth direction.

17. An object holder according to claim 11, wherein the fifth connection is flexible at least along the third press direction at a limited change of extension along the fifth direction.

18. An object holder according to claim 11, wherein

the fourth connection is rigid,

the fifth connection is flexible along the third press direction at a limited change of extension along the fifth direction,

the fifth connection is also flexible along the fourth direction and

the sixth connection is flexible along the the fourth direction.

19. An object holder according to claim 11, wherein the third displacement is smaller than the fourth displacement.

20. An object holder according to claim 11 or 12, wherein a slide is integrated with the object space during manufacturing.

21. An object holder according to claim 11 or 12, wherein a slide can be attached to the object space.