NL2030512B1 - A movement platform for microscopic slide positioning - Google Patents

Abstract

We describe a positioning platform for low-cost microscope slide scanner with movement of the slide controlled by servo motors. The slide holder (sample holder) is attached to the servo’s by means of crank mechanisms, whereas the number of controller servos is equal to the number of degrees of freedom of the slide holder. The movement of the sample holder is achieved by simultaneous independent control of all servos. The remaining degrees of freedom of the sample holder are restricted with regard to the base by sliding screws and magnets, providing the necessary pressure to keep the holder supported by the screws on top of the base regardless of the system position. Furthermore said screws facilitate the adjustment of the sample tip and tilt with respect to the base.

Description

A movement platform for microscopic slide positioning

The present invention relates to a movement platform for microscopic slide positioning, in particular to a positioning device of the type to position a microscopic glass slide.

This automated positioning system for microscopic glass slides relates to microscopic imaging, specifically to an improved system to automatically position a microscopic slide under an objective and adjust this position in a mechanical way.

When microscopy was invented in 1590 by Hans and Zacharias Janssen (Orchard 2014), it was made possible to study microorganism and even smaller objects. This technique was adopted by the healthcare sector in order to diagnose parasitic diseases amongst others. In order to diagnose by means of microscopy a blood smear placed on a glass slide should be studied. To diagnose if a person is contaminated with a microorganism, a large area of this blood smear should be investigated. However when using a microscope, a limited part of the blood smear can be shown in detail at once due to the limitations of microscopy. So in order to study multiple adjacent placed areas of a blood smear, the place of the blood smear and the microscope should be adjusted with regard to each other.

Originally this was done by moving the glass slide manually. This is a very time consuming process requiring high educated qualified personnel, making diagnosis by means of microscopy a very costly process, prone to human mistakes. So automatic microscopic devices are developed. These devices can scan and image blood smears without human interference. This increases the speed and accuracy of scanning. However these devices make use of expensive hardware, making these devices not suitable for low resource settings. Therefore a movement platform is developed making use of simple cheap hardware. This makes diagnostics via microscopy more accessible all over the world.

Motorized linear stages of Zaber provide orthogonal linear movement in a range of hundreds of millimeters with micrometer precision. However, these solutions are not applicable to low-cost scanning microscopes due to very high mechanical complexity, extremely high precision and very high price. https://www.zaber.com/

Patent application JP2019056917A describes the general principle of a three- dimensional scanner without any particular claim to novelty.

Invention US6310342B1 describes the scanning probe microscope stage, which is not directly applicable to medical scanners that need to provide scan fields of tens of mm.

In the invention US5360974A a dual quad flexure scanner for a microscope includes dual quad flexure carriage and assembly, for receiving a sensing probe, is used for scanning the sensing probe across a target surface. Using flexures and piezo actuators provides high scanning precision, but results in limited scanning range and high price of the scanner. Also, piezo actuators possess strong hysteresis and can be linearized only with active feedback.

As seen, in most prior designs, the horizontal scanning in the plane X-Y, orthogonal to the optical axis Z is achieved with a very high precision, preserving the Z position and providing submicron precision in the X-Y plane. In fact, scanning for infection diseases, blood analysis, etc, does not require a very precision positioning in X-Y plane, as each new scan should provide a new field of view without any reference to the previous field. The operation of merging the fields is not performed, as it is not necessary. Therefore, to our knowledge, a high-speed scanner providing a large scanning field with relatively low precision in the X-Y plane and preserving high precision in the Z direction is of a great interest and has not been reported in the patent literature, to our knowledge.

Objects and advantages

Accordingly, several objects and advantages of the automated positioning system for microscopic glass slides are that the process of positioning a glass slide is automated and thus do not require a highly trained microscopist to position the glass slide to different areas under the microscope objective. Secondly, automating the scanning increases the efficiency of a diagnostic staff worker, whereas he can work on other tasks while the positioning device is working. Also, the automated positioning system eliminates human scanning errors. Next to that, the developed system consists out of cheaper components than existing automated positioning systems.

Other objects and advantages are the possibility to fabricate and assemble the scanner in a low-resource setting with a variety of technologies, ranging from turning and milling, to 3D printing .

Other objective is the low price of the actuators and control systems, that allows for serial and mass production of the scanner in a low-resource environment.

Further objects and advantages of the automatic positioning table will become apparent from a consideration of the drawings and ensuing description.

Summary of the invention

A microscope stage, including orthogonal X and Y directions in the plane of the sample, represented for instance by the glass slide with blood smear, and Z direction, co-incident with the optical axis of optical microscope objective, and orthogonal to said X and Y directions, capable of X-Y movement, preserving the Z position of the sample, is provided. The stage includes optical window for illumination and observation of the sample, and the flat magnetic base fabricated of magnetically soft material, serving as the limiter for three degrees of freedom of said stage, namely the base plate limits the translation of the stage in the Z direction, and rotations around the X and Y axes. Said translating stage is connected (pressed to ) to the base by a plurality of permanent magnets, providing necessary pressure to keep the stage in contact with the base. The said pressure can also be provided by an arbitrary spring loaded mechanism. A projection of the force produced by said spring mechanism acts in the direction orthogonal to the base, to keep the platform in contact with the base. The other projection of the force produced by the spring mechanism acts in the plane of X-Y movement, to eliminate the back lash in the crank mechanisms. The rotation around X, rotation around Y and translation along the Z axis degrees of freedom are limited by three sliding screws that define the initial position of the stage with respect to said degrees of freedom. Said stage possesses a freedom to be moved on the surface of the base, with three unrestricted degrees of freedom, namely translation X, translation Y and rotation around the axis Z, controlled by a plurality of crank mechanisms driven by rotation motors. For unique definition of the positions defined by said crank mechanisms, the rotation of motors can be limited to 180 degrees.

The three degrees of freedom, namely Z translation and X,Y rotations are restricted by the sliding screws supported by the base plate. The actuation scanning mechanism defines the position of the stage with respect to three remaining unrestricted degrees of freedom, namely the plane-parallel movement along X and Y directions, and the rotation of the stage around Z axis. Any other orthogonal and non-orthogonal coordinate system can be used to provide and describe this motion. Any actuation mechanism providing nonlinear but linearly independent movement within the said unrestricted degrees of freedom can be used for stage positioning. Our invention provides the inexpensive way to obtain quick and precise positioning of the sample table by using of low-cost non- orthogonal mechanical actuators for precise unambiguous definition of the lateral and angular position of the sample table. The number of actuators used in the mechanism should be equal to the number of unrestricted degrees of freedom. In particular case, the three supporting sliding screws restrict three degrees of freedom, therefore three independent actuators are needed for unambiguous definition of the mechanical system and providing the necessary movement along three coordinates, of which two are translational, along X and Y axes, and one is rotational, around the Z axis.

The other type of a non-orthogonal nonlinear actuator for a single degree of freedom is illustrated in Fig. 4 in a coordinate system formed by X-axis 51 and Y- axis 53. The actuator comprises a Servo motor 52, possessing a Rotating shaft 50 with position X1,Y1 and rotation angle f limited to rotation range of Rotating shaft 50. A Horn 55 with length Lh and a Beam 56 with length Lb. There is a one-to one correspondence between the position of a Beam end 57, Xc Yc and the shaft rotation defined by an Angle 54. This relation is obtained by solving the system of quadratic equations: (x-xc)2+(y-yc)"2=LDb, (x-x1)*2+({y-y1)*2=Lh (1)

For x and y, where x and y are the coordinates of the interconnection between Horn 55 and Beam 57. Further, the angle of horn rotation f is given by: f=atan2(x-x1,y-y1) (2)

The angle of rotation of the horn is defined by solving the system (1) for x and y, and then calculating the angle using expression (2). The system (1,2) has two different solutions, however it does not lead to any instability if the range of rotation of Rotating shaft 50 is limited to 180 degrees and the starting position of Beam 56 5 is co-incident with the direction of Y-axis 53.

The crank system comprised of a single servo with horn and beam limits one degree of freedom. To obtain precision positioning of the stage in three coordinates, three nonlinear actuators need to act on the stage in three different points, fully defining the stage position in space, as shown in Fig. 1. Three degrees of freedom are limited by the sliding screws and the base, the remaining three degrees of freedom are defined by the nonlinear actuators according to expressions (1) and (2).

The invention Is not limited to the implementation with servos, beams and horns.

Any set of non-orthogonal actuators acting on the stage in three different points would provide the necessary movements within the available degrees of freedom. .

Possible implementation of such a non-orthogonal system is the system with spiral cams connected to servo motors. Each cam provides for movement in one degree of freedom, wherein three motors with three cams would provide for complete positioning in X-Y plane and rotation around the Z axis.

The choice of servos with beams and horns, as described further, is decided by the available speed, precision and price of the actuators and the simplicity of implementation.

The invention will now be elucidated on the basis of non-limitative exemplary embodiments which are illustrated in the following figures. The invention is illustrated but not limited by this description.

Fig. 1 is a front view of one possible implementation of the automated positioning table;

Fig.2 is a side view of one possible implementation of the automated positioning table;

Fig.3 is a cross section of one possible implementation of the automated positioning table. The cross section is derived from Fig. 1, indicated by the section lines 3-3.

Fig. 4 contains the illustration of the crank mechanism;

Fig. 1 shows the front view of an automated position table. It consists out of a

Microscope breadboard 25 on which a Servo plate holder 34 is mounted by means of bolts (Fig. 2). Microscope breadboard 25 can be made in any size from stiff material that is in the same order of magnitude of the Young's modulus of the used

Anodized aluminum. The function of this base is to stabilize the automated positioning device. Holes in this base in order to mount Servo base holder 34 can be made by machining, milling, drilling etc. The holes can be smooth or threaded.

Servo base holder 34 is a stiff structure made from Anodized Aluminum, but can be made from any stiff material. It connects a Servo base 20 to Microscope breadboard 25. Servo base holder 34 is attached to both parts by means of bolts.

This connection can also be made by means of other fasteners but not limited to fasteners only.

On this Servo base 20 a Servo 13, a Servo 17 and a Servo 24 is attached by means of, but not limited to bolts. The holes on Servo base 20 are threaded holes, however they could also be smooth. Servo base 20 is flat and is made from stiff magnetically soft metal. This material can be any material that can be magnetized.

Servo base 20 has sunk holes without screw thread to make sure that bolt heads of bolts that are needed to attach Servo base 20 to a Servo base holder 34 do not stick out the surface of Servo Base 20. However these sunk holes are not needed in the case the screw holes are located somewhere else on Servo base 20, or if

Servo base holder 34 is attached to Servo base 20 in another way.

Servo 13, 17, 24 have a range of 180 degrees.

On Servo 13, a Horn 12 is attached by clamping it around Servo 13. Horn 12 can be attached to Servo 13 by means of formfitting the one end of the rectangular shape around the rotational part of Servo 13. This shape could also be circular, square or triangle. However Horn 12 can also be attached in other ways to Servo 13. For example Horn 12 can be, but not limited to, screwed, glued or clamped to

Servo 13. Servo 13 should be rotated to its maximum orientation clockwise when

Horn 12 is attached vertically to Servo 13. In the other side of the rectangular shape a hole with screw thread is made. This hole could also be without screw thread. Furthermore, in another embodiment the hole could even not be present and an axis could be present fixed to Horn 12. Horn 12 is made of Anodized

Aluminum, but can also be made of, but not limited by, any plastic or other metal.

Horn 12 is attached to a Beam 10 by means of an Axis 11. The shape of Beam 10 is rectangular with a hole with screw thread on both ends. However this shape could also be circular, square or triangle. This screw thread has the same diameter as the screw thread in Horn 12. This hole could also be without screw thread.

Furthermore, in another embodiment the hole could even not be present and an axis could be present fixed to Beam 10. Beam 10 is made of Anodized Aluminum, but can also be made of, but not limited to, any plastic or other metal.

Axis 11 is an axis with screw thread which fits with one end in a hole with screw thread in Horn 12, on the other end in the hole with screw thread of Beam 10.

Screw thread is present in these holes and on the axis in order to limit play in a cheap way. This play would be present in cheap produced axis and holes. Horn 12 and Beam 10 are attached by Axis 11 at a distance of at least one revolution of the screw thread. In another embodiment, Axis 11 could be a rod without screw thread.

Secondly Axis 11 could be fixed to Horn 12 or Beam 10. The material of Axis 11 is metal, but is not limited to metal.

Beam 10 is attached to a Sample holder 33 by means of an Axis 32. Axis 32 is an axis with screw thread which fits with one end in a hole with screw thread of Beam 10. The other end fits in a hole with screw thread in Sample holder 33. In another embodiment, Axis 11 could be a rod without screw thread. Secondly Axis 11 could be fixed to Sample holder 33 or Beam 10. The distance between Beam 10 and

Sample holder 33 is such that the bottom of Sample holder 33 is pressed against the top of Servo base 20. The material of Axis 32 is metal, but is not limited to metal.

On Servo 17, a Horn 16 is attached by clamping it around Servo 17. Horn 16 is equal in shape as Horn 12. In another embodiment the horns could differ from each other in form, shape or material. This shape could also be circular, square or triangle. Horn 16 can be attached to Servo 17 by means of formfitting the one end of the rectangular shape around rotational part of Servo 17. However Horn 16 can also be attached in other ways to Servo 17. For example Horn 16 can be, but not limited to, screwed, glued or clamped to Servo 17. In the other side of the rectangular shape a hole with screw thread is made. This hole could also be without screw thread. Furthermore, in another embodiment the hole could even not be present and an axis could be present fixed to Horn 16. Horn 16 is made of

Anodized Aluminum, but can also be made of, but not limited by, any plastic or other metal.

Horn 16 is attached to a Beam 14 by means of an axis 15. The shape of Beam 14 is rectangular with a hole with screw thread on both ends. However this shape could also be circular, square or triangle. This screw thread has the same diameter as the screw thread in Horn 16. This hole could also be without screw thread.

Furthermore, in another embodiment the hole could even not be present and an axis could be present fixed to Beam 14. Beam 14 is equal in shape as Beam 10, however can also differ from each other in form, shape or material. Beam 14 is made of Anodized Aluminum, but can also be made of, but not limited to, any plastic or other metal.

Axis 15 is an axis with screw thread which fits with one end in a hole with screw thread in Horn 16, on the other end in the hole with screw thread of Beam 14.

Screw thread is present in these holes and on the axis in order to limit play. This play would be present in cheap produced axis and holes. Horn 16 and Beam 14 are attached by Axis 15 at a distance of at least one revolution of the screw thread. In another embodiment, Axis 15 could be a rod without screw thread. Secondly Axis 15 could be fixed to Horn 16 or Beam 14. The material of Axis 15 is metal, but is not limited to metal.

Beam 14 is attached to a Sample holder 33 by means of an Axis 29. Axis 29 is an axis with screw thread which fits on the one end in a hole with screw thread of

Beam 14. The other end fits in a hole with screw thread in Sample holder 33. In another embodiment, Axis 15 could be a rod without screw thread. Secondly Axis 15 could be fixed to Sample holder 33 or Beam 14. The distance between Beam 14 and Sample holder 33 is such that the bottom of Sample holder 33 is pressed against the top of Servo base 20. The material of Axis 29 is metal, but is not limited to metal.

On Servo 24, a Horn 23 is attached by clamping it around Servo 24. Horn 23 can be attached to Servo 24 by means of formfitting one end of the rectangular shape around rotational part of Servo 24. This shape could also be circular, square or triangle. However Horn 23 can also be attached in other ways to the Servo 24. For example Horn 23 can be, but not limited to, screwed, glued or clamped to Servo 24.

Servo 13 should be rotated to its maximum orientation clockwise when Horn 12 is attached horizontally to Servo 24. In the other side of the rectangular shape a hole with screw thread is made. This hole could also be without screw thread.

Furthermore, in another embodiment the hole could even not be present and an axis could be present fixed to Horn 23. Horn 23 is made of Anodized Aluminum, but can also be made of, but not limited by, any plastic or other metal.

Horn 23 is attached to a beam 22 by means of an axis 21. The shape of Beam 22 is rectangular with a hole with screw thread on both ends. However this shape could also be circular, square or triangle. This screw thread has the same diameter as the screw thread in Horn 23. This hole could also be without screw thread.

Furthermore, in another embodiment the hole could even not be present and an axis could be present fixed to Beam 22. Beam 22 is made of Anodized Aluminum, but can also be made of, but not limited by, any plastic or other metal.

Axis 21 is an axis with screw thread which fits on the one end in a hole with screw thread in Horn 23, on the other end in the hole with screw thread of Beam 22.

Screw thread is present in these holes and on the axis in order to limit play. This play would be present in cheap produced axis and holes. Horn 23 and Beam 22 are attached by Axis 21 at a distance of at least one revolution of the screw thread. In another embodiment, Axis 21 could be a rod without screw thread. Secondly Axis 21 could be fixed to Horn 12 or Beam 10. The material of Axis 21 is metal, but is not limited to metal.

Beam 22 is attached to a Sample holder 33 by means of an Axis 26. Axis 26 is an axis with screw thread which fits on the one end in a hole with screw thread of

Beam 22. The other end fits in a hole with screw thread in Sample holder 33. In another embodiment, Axis 26 could be a rod without screw thread. Secondly Axis 26 could be fixed to Sample holder 33 or Beam 22. The distance between Beam 22 and Sample holder 33 is such that the bottom of Sample holder 33 is pressed against the top of Servo base 20.The material of Axis 26 is metal, but is not limited to metal.

Sample holder 33 is a part that is able to hold a sample that can be investigated by means of microscopy. Sample holder 33 has a rectangular shape. The shape of this Sample holder is not limited to a rectangle, but could also be a oval, square or triangle. It has three holes with screw thread on a horizontal line with regard to each other to attach Axis 26, 29 and 32. However the placing and the amount of holes can vary. The distance between holes to attach Axis 29 and Axis 32 is equal to the distance between Axis 11 and 15 in order to hold Sample holder 33 in horizontal position. In other designs, this distance could very. Furthermore Sample holder 33 has three threaded holes for an Adjustment screw 19 an Adjustment screw 28 and an Adjustment screw 30 (Fig. 2). The amount and placing of

Adjustment screws can vary in another embodiment. Inside the triangle these

Adjustment screws form together, three holes with a bottom for a Permanent magnet 18, a Permanent magnet 27 and a Permanent magnet 31 are present. The holes for said Permanent magnets could also be placed out of the triangle. The amount of said Permanent magnets can vary. The distance between the bottom of the holes for Permanent magnets 18, 27 and 31 and the bottom of Sample holder is 0,5 mm (Fig.3), but this distance can vary in other designs. Sample holder 33 is made from anodized Aluminum, but can be made from, but not limited to, any other metal or plastic.

The material of Adjustment screws 19, 28 and 30 is, but not limited to, metal. The screws stick out of the bottom side of Sample holder 33 and press with the ending of the screw against Servo base 20. Adjustment screws 19, 28 and 30 can also have another embodiment than screws. It can be an axis, wedge or another kind of mechanism.

Permanent magnets 18, 27 and 31 are cylindrical with a height of 5mm and a diameter of 5mm. These magnets are nickel-plated (Ni-Cu-Ni} magnets with a holding force of 0,8 kg — available from Magnetenspecialist. However, the magnets can be of any size and have any holding force that is able to press Sample holder 33 to Servo base 20. Permanent magnets 18, 27 and 31 are glued in the holes in

Sample holder 33 in order to keep them in place. Holding these magnets in place can also be done by, but not limited to, screws or other fasteners

The movement of the Sample holder 33 is needed in order to change the area of view that can be seen on the microscope. The linearity of this movement is important because it increases the ease of use of the device. Servo's 13, 17 and 24 are controlled by software. In order to move Sample holder 33 in a linear way — e.g. back to front, left to right, all three Servo’s have to work together. Servo 13 and 17 will move in synchrony with each other (Servo A rotation 40 and Servo B rotation 41 Fig. 1). Servo 24 will rotate (Servo C rotation 42 Fig. 1) in relation to Servo 13 and 17 according to the formula in Fig. 3. The rotation angles of all three servos are calculated by the control software implementing relations (1) and (2). This control allows to realize any movement of the sample including translations along X and Y axes, and rotation around the Z axis. The ranges of movement are limited by the design parameters of the table, the lengths of horns and beams, which can be chosen individually for each servo.

In one particular implementation, the relation in movement of Servo 13 and 17 with regard to Servo 24, as explained above, takes care that Sample Holder 33 moves in a linear way

Adjustment screws 19, 28 and 30 are used to align the plane of Sample holder 33 parallel and perpendicular to Microscope breadboard 25. Turning one of the adjustment screws changes the length the screw sticks out of the bottom side of

Sample Holder 33. So the screw presses Sample holder 33 further away or closer to Servo base 20. This results in a change in orientation of the plane of Sample holder 33.

In order to keep the plane of Sample holder 33 stable, Permanent magnets 18, 27 and 31 push Sample holder 33 towards Servo base 20. This makes sure that the plane of Sample holder 33 is aligned with regard to Servo base 20 by taking into account the length of the adjustment screws.

Axis 11, 15, 21, 26, 29 and 32 are axis with screw thread in the described embodiment. Another embodiment of these axis are that the axis are without screw thread, but are smooth. In that case the holes in beams 10, 14, 22 and the holes in horns 12, 16 and 23 would also have no screw thread, but be smooth.

Servo 13, 17 and 24 are in the described embodiment metal geared Servo’s. In another embodiment, These Servo’s could be changed for any kind of motor or servo. All servos can be controlled separately, to provide two translational and one rotational degrees of freedom to the movement of the sample.

In another embodiment the force needed to press Sample holder 33 to the surface of Servo base 20 can be delivered by springs or another kind of mechanism.

While the above description contains many specificities, these should not be construed as limitations on the scope of the automated positioning system for microscopic glass slides, but rather as an exemplification of one preferred embodiment thereof. Many other variations are possible.

For example all kind of different materials that could be used to make the parts.

Next to the metals and plastics often mentioned, most parts could also be made from wood, bamboo, composites etc. Furthermore the sizes or shape of the described parts could differ. The beams and horns could be made oval, round, triangular etc. Also the servo base could be massive, have a grid etc. Next to that, parts can be attached to each other by other means than screws like glue, snap

Hits, form fitting etc. Lastly the axis’ could be left out and another mechanism to let the horns and beams rotate with regard to each other could be implemented.

Accordingly, the scope of the automated positioning system for microscopic glass slides should be determined not by the embodiment illustrated, but by the appended claims and their legal equivalents.

List of reference numerals in Fig. 1-3. 10. Beam 11. Axis 12 Horn 13. Servo 14. Beam 15. Axis 16. Horn 17. Servo 18. Permanent magnet 19. Adjustment screw 20. Servo base 21. Axis 22. Beam 23. Horn 24. Servo 25. Microscope breadboard 26. Axis 27. Permanent magnet 28. Adjustment screw 29. Permanent magnet 30. Axis 31. Sample holder 32. Servo base holder 40. Servo rotation 41. Servo rotation 42. Servo rotation

List of reference numerals in Fig. 4 50. Rotating shaft 51. X-axis 52. Servo motor 53. Y-axis

54. Angle 55. Horn 56. Beam 57. Beam end

Claims (10)

Conclusions A positioning device of the type for positioning a microscopic slide, comprising: a sample holder with six degrees of freedom and optical window, b. a flat magnetic base with optical window, C. multiple magnets to hold the sample holder pressed against the base, d. multiple setscrews to limit X and Y rotation and Z translation of the holder relative to the base, e. several rotary motors attached to the base, f. a plurality of horns and beams forming crank systems for converting the rotary motion of said motors into translation of said sample holder along the X and Y axes, and rotation of said sample holder about the Z axis. The positioning apparatus according to claim 1, wherein two rotational and one translational degrees of freedom of the sample holder are set by three adjusting screws, and the other three degrees of freedom are fixed by the position of three motor controllers. Positioning device according to claims 1 and 2, wherein said movement of the sample holder is achieved by means of three spiral cams connected to the three control motors. A positioning device according to claims 1 and 2, wherein said movement of the holder is achieved by means of three crank systems formed by horns and beams connected to three control motors. A positioning device according to claim 4, wherein each crank system consists of a horn rigidly connected to the motor shaft and a beam hingedly connected to the free end of the horn on one side and to the moving holder on the other. other side. A positioning device according to claim 5, wherein the range of rotation of the control motor is 180 degrees. A positioning device according to claim 4, wherein three said motors are controlled by an algorithm described by (1) and (2). A positioning device according to claim 4, having two degrees of freedom, wherein two of said three motors have an identical crank system and are controlled by the same control signal. A positioning device according to claim 4, wherein said motors are controlled by an algorithm described by (1) and (2). The positioning apparatus of claim 1, wherein the position of said sample holder relative to the servo base is controlled by the plurality of adjusting screws and said plurality of magnets.