WO2021104776A1

WO2021104776A1 - A control unit for focusing a sample and a method thereof

Info

Publication number: WO2021104776A1
Application number: PCT/EP2020/080053
Authority: WO
Inventors: Deivasegamani VINOD KUMAR; Vikrant Raghu; Parthasarathy RAHUL SAI; Krishnan Venkataraman
Original assignee: Robert Bosch Gmbh; Robert Bosch Engineering And Business Solutions Private Limited
Priority date: 2019-11-29
Filing date: 2020-10-26
Publication date: 2021-06-03
Also published as: KR20210067937A

Abstract

The control unit (10) adapted to identify multiple zones (14) to focus in the sample (12) and to control a movement of an objective lens (16) over at least one zone (14)(a) of the sample (12) in a predefined distance range from the sample (12). The control unit (10) further adapted to detect a focused point within the predefined distance range corresponding to the at least one focused zone (14) (a) of the sample (12). The control unit (10) determines a new distance range to focus the objective lens (16) over at least one next zone (14) (b) of the sample (12), from the detected focused point The control unit (10) detects a new focused point within the new distance range corresponding to the at least one next zone (14) (b) of the sample (12). The focus on the sample (12) in the perpendicular (z-axis) direction is more precise and obtained with ease.

Description

THE PATENTS ACT, 1970 (39 of 1970) & The Patents Rules 2003 COMPLETE SPECIFICATION

(SECTION 10 and Rule 13)

1. Title of the Invention:

A control unit for focusing a sample and a method thereof

2. Applicants: a. Name: Robert Bosch Engineering and Business Solutions Private Limited

Nationality: INDIA

Address: 123, Industrial Layout, Hosur Road, Koramangala, Bangalore - 560095, Karnataka, India b. Name: Robert Bosch GmbH Nationality: GERMANY Address: Feuerbach, Stuttgart

Complete Specification:

The following specification describes and ascertains the nature of this invention and the manner in which it is to be performed.

Field of the invention

[0001] This invention is related to a control unit for focusing a sample and a method thereof.

Background of the invention

[0002] The microscopic lens is used to produce magnified images that are too small to seen by unaided eye. The lens provides the enlarged view that helps in examining and analyzing the image. The actuator used in the applications like microscope, semiconductor chip manufacturing, optical industries, operates in micrometer accuracy & motor feedback system needs very high precision feedback system. There are encoder feedback systems for the actuator used in those kind of applications. A run out in the stage of automated microscope causes unwanted vibrations, which shifts the focusing point in the z-axis. This causes the requirement to focus again whenever the FOV (Field ofView] changes. The more a focusing point shifts, the more time ittakes to focus itback. Usually the motor and its mechanical set up are built using very high precision manufacturing and assembly. Such motor set ups are intricate and have complexity in designing. In other cases, separate level maintaining electromechanical set ups are designed which have sensors that sense the horizontality and feed it to the z-axis motors to maintain the level.

[0003] A prior art document US2017299553 discloses an autofocus method for microscope and microscope comprising autofocus device. The device comprises microscope including an objective having a focal plane in a sample space and a light modulator for generating a luminous modulation object that is intensity-modulated periodically along one direction. An autofocus illumination optical unit that images the modulation object such that its image arises in the sample space. An autofocus camera and an autofocus imaging optical unit that images the image of the modulation object in the sample space onto the autofocus camera. A control device, which receives signals of the autofocus camera, determines an intensity distribution of the image of the modulation object, and generates a focus control signal therefrom. Brief description of the accompanying drawings

[0004] Figure 1 illustrates a control unit for focusing on a sample, in accordance with an embodiment of the invention;

[0005] Figure 2 illustrates a focusing system, in accordance with an embodiment of the invention; and

[0006] Figure 3 illustrates a method of focusing a sample in accordance with the invention.

Detailed description of the embodiments

[0007] Figure 1 illustrates a control unit for focusing a sample, in accordance with an embodiment of the invention. The control unit 10 adapted to identify multiple zones 14 to focus in the sample 12 and to control a movement of an objective lens 16 over at least one zone 14 (a] of the sample 12 in a predefined distance range from the sample 12. The control unit 10 further adapted to detect a focused point within the predefined distance range corresponding to the at least one focused zone 14(a] of the sample 12. The control unit 10 determines a new distance range to focus the objective lens 16 over at least one next zone 14(b] of the sample 12, from the detected focused point The control unit 10 detects a new focused point within the new distance range corresponding to the at least one next zone 14(b] of the sample 12.

[0007] Figure 2 illustrates a focusing system, in accordance with an embodiment of the invention. The focusing system 11 comprises a sample holder 13 having a sample 12. The focusing system 11 comprises an objective lens 16 positioned above the sample holder 13. The system 11 further comprises an actuator 18 connected to the objective lens 16, and the actuator 18 is adapted to adjust the objective lens 16 over the sample 12. The system 11 comprises the control unit 10 electronically connected to the actuator 18. The control unit 10 adapted to identify multiple zones 14 to focus in the sample 12 and to control a movement of an objective lens 16 over at least one zone 14(a] of the sample 12 in a predefined distance range from the sample 12. The control unit 10 further adapted to detect a focused point within the predefined distance range corresponding to the at least one focused zone 14(a] of the sample 12. The control unit 10 determines a new distance range to focus the objective lens 16 over at least one next zone 14(b] of the sample 12, from the detected focused point The control unit 10 detects a new focused point within the new distance range corresponding to the at least one next zone 14(b] of the sample 12.

[0008] The objective lens 16 is fitted into an opening of an objective holder 24 in the focusing system 11. The objective lens 16 is adapted to focus on different portions of the sample 12 to identify the contents of the sample 12. The objective holder 24 along with the objective lens 16 is moved/adjusted in a perpendicular (such as z-axis] direction with respect to the sample 12 during focusing on at least one portion of the sample 12. The sample 12 is placed in the sample holder 13 in a planar positon in the focusing system 11. The sample holder 13 is further connected to a first motor assembly 20 and a second motor assembly 22 of the focusing system 11, for adjusting the sample holder 13 in the x- axis direction and the y-axis direction respectively. It is to be noted that, the first motor assembly 20 and the second motor assembly 22 are called as first stage and the second stage from hereon in the present disclosure.

[0009] The actuator 18 and the control unit 10 are positioned in a housing 26 of the focusing system 11. The movable objective holder 24 is connected to the actuator 18 via a mechanical arrangement According to one embodiment of the invention, the focusing system 11 is a microscopic device that is used to focus a sample having a human biological specimen. The focusing system 11 is not restricted to the microscopic device as disclosed above, but the same is applicable for any of the focusing systems, where there is a requirement to focus on a sample 12. The sample 12 is not restricted to a structure having the human biological specimen, but can be any other sample like a semiconductor chip, an optical fiber as known to a person skilled in the art

[0009] According to one embodiment of the invention, the actuator 18 is a linear actuator. However, the actuator 18 is not restricted to a linear actuator, but can be any actuator chosen from a group of actuators comprising a piezo-electric actuator, a hydraulic actuator and the like. The sample 12 comprising the human biological specimen is any material derived from a human body comprising blood, urine, tissues, organs, saliva, DNA/RNA, hair, nail clippings, cell tissues, or any other fluids as known in the state of the art

[0010] A mechanical arrangement present between the objective lens 16 (fitted in the objective holder 24] and the actuator 18 is an inverted L-shaped plate 28 and a guide rail assembly 30. The actuator 18 connected to the inverted L-shaped plate 28 via a movable pin 32 and which in turn is connected to the movable objective holder 24 having the objective lens 16. The guide rail assembly 30 is connected between the inverted L- shaped plate 28 and the movable objective holder 24. The actuator 18, the movable pin 32, the inverted L-shaped plate 28, the guide rail assembly 30 and the movable objective holder 24 are connected mechanically, thus the movement of the one component causes a simultaneous movement in all the connected components.

[0011] For instance, when the control unit 10 operates the actuator 18, the movement of a shaft of the actuator 18, moves the movable pin 32 by which , the inverted L- shaped plate 28 and the objective holder 30 position is adjusted on the sample 12 . The objective holder 24 along with the objective lens 16 moves in the perpendicular direction with reference to the sample 12.

[0012] When the focusing system 11 is under operating condition, the sample holder 13 experiences vibrations due to the movement of either one of the first stage 20 or the second stage 22 connected to the sample holder 13. The focusing by the objective lens 16 on the content of the sample 12 is not accurate due to these vibrations of the first stage 20 and the second stage 22. In order to compensate these vibrations, the control unit 10 identifies multiple zones on the sample to focus one at each time. The control unit 10 as disclosed in the present disclosure is chosen from a group of control units comprising a microprocessor, a microcontroller, a digital circuit, an integrated chip and the like. The movement of the objective lens 16 on the sample 12 is measured in the form of the distance from the sample 12.

[0013] Figure 3 illustrates a method of focusing a sample 12, accordance to the present invention. In step SI, the multiple zones 14 are identified to focus in the sample 12. In step S2, a movement of the objective lens 16 is controlled over at least one zone 14 (a] of the sample 12 in a predefined distance range from the sample 12. In step S3, a focused point is detected within the predefined distance range corresponding to the at least one focused zone 14(a] of the sample 12. In step S4, a new distance range to focus the objective lens 16 over at least one next zone 14 (b] of the sample 12, from the detected focused point In step S5, a new focused point is detected within the new distance range corresponding to the atleastone next zone 14 (b] ofthe sample 12.

[0014] The method of focusing the sample 12 is explained in detail. The sample 12 when loaded into the sample holder 13 in the planar position, the control unit 10 identifies multiple zones 14 on the sample 12. According to one embodiment of the invention, the identified zones 14 are have same surface area. According to another embodiment of the invention, the control unit 10 identified zones 14 have different surface areas. The control unit 10 selects one zone for initial focus of the objective lens 16 during the start of the focusing system 11. The control unit 10 determines a predefined distance range for the objective lens 16 to focus on the selected zone. The predefined distance range is a distance from the sample 12 up to a maximum position of the objective lens 16 in the z-axis. In another words, the predefined distance range is with reference to the sample 12

[0015] The predefined distance range is from zero to a maximum distance of the objective lens 16 that can go in the z-axis. For the first selected zone, the control unit 10 moves/adjusts the objective lens 16 over the sample 12. Upon detecting a focused point/plane from the sample 12 within the predefined distance range, the control unit 10 moves the objective lens 16 to the next zone on the sample 12. For focusing on the content of the sample 12, the control unit 10 determines a new distance range from the detected focused point of the previous selected zone 14(a] The detected focused point becomes the average point for the new distance range of the next zone 14(b] .

[0016] The control unit 10 computes (adds and subtracts] a predefined value to the detected focused point of the previously selected zone to determine the new distance range for the next zone. In other words, the control unit adds the positive and negative value of the predefined value to the detected focused point. Upon computing the new distance range for the next zone, the control unit 10 adjusts the objective lens 16 over the next zone of the sample 12 within the new distance range to detect a new focused point. The new detected focused point becomes an average point for the further next zone of the sample 12. The same process is followed for all the identified zones 14 of the sample 12. The control unit 10 upon completing the above-disclosed process, the focused content of the sample 12 is displayed as an image in a processing device 34.

[0017] The above method is explained with an example. A sample 12 having at least one specified human biological specimen is loaded into the sample holder 13. The control unit 10 identifies the multiple zones 14 on the sample 12 for focusing. For instance, the control unit 10 identifies three zones on the sample 12 for focusing. The control unit 10 adjusts the objective lens 16 on the first zone within the predefined distance range i.e., from 0-100 microns from the sample 12. Wherein the maximum distance the objective lens 16 that can be moved from the sample 12 in the z-axis direction is lOOmicrons. The control unit 10 detects a focused plane in the 0-100 microns distance range at 50^th micron. The control unit 10 moves the objective lens 16 onto the second zone of the sample 12 to focus the content of the sample 12. The control unit 10 computes a new distance range for the second zone by considering the detected focused point of the first zone as an average point, i.e. the 50 micron.

[0018] The control unit 10 computes the new distance range for the second zone by adding and subtracting a predefined value of 25 microns to the detected focused point (i.e., 50^th micron]. The new distance range for the second zone is computed as 50 +25 = 75microns and 50-25 = 25microns. The new distance range of the second zone is 25-75 microns. The control unit 10 adjusts/moves the objective lens 16 in the 25-75 microns range to detecta focused plane for the second zone. The control unit 10 detects a focused point in the second zone at 40^th micron. The control unit 10 upon detecting the new focused point for the second zone moves the objective lens 16 onto the third zone.

[0019] The new distance range for the third zone is computed by adding and subtracting 25 microns to the 40 (the detected focused point of the second zone]. The new distance range for the third zone is computed as 40+25 = 65 and 40-25 =15, which becomes IS OS. The control unit 10 moves/adjusts the objective lens in the new distance range 15- 65 microns in the third zone to detect a new focused point in the third zone. The control unit 10 detects a new focused point at 30^th micron for the third zone. Upon detecting the best- focused point, the focused image of the content of the sample 12 is displayed in the processing device.

[0020] The device 10 is electronically connected to a processing device 34 to display the focused portion of the sample 12. The processing device 34 is a computer according to one embodiment of the invention. However, the processing device 34 is not restricted to computer, but can be any processing device 34 that comprises a display. The control unit 10 actuates the actuator 18 by providing a single signal or plurality of signals based on the portion of the sample 12 to be focused.

[0021] For instance, if there is a requirement of a more precised image of the sample 12 to be focused or if the focus on the image needs to be maximized, then the control unit 10 provides plurality of signals to the actuator 18 for adjusting the movement of the movable objective holder 24. The control unit 10 provides approximately sixteen continuous signals to the actuator for moving the objective lens 16, to 25 microns for focusing on the portion of the sample 12, and image is displayed in the processing device 34. In another instance, the control unit 10 provides a single signal to the actuator 18, for fine moving objective lens 16 to 1.6 microns and the focused image is displayed in the processing device 34.

[0022] With the above-disclosed control unit 10 and the method, the vibrations developed due to the movement of the first stage 20 and the second stage 22 on the sample holder 13 is reduced. The focus on the sample 12 in the perpendicular (z-axis] direction can be controlled automatically in the processing device 34. The focus can be more precise, based on the requirement with ease and without any extra component The automatic adjustment of the objective lens 16 over the sample 12 provides a cost- effective, less strain solution for the people working in the medical labs, semiconductor industries (in chip making process], in optical industries and the like, as it reduces the human intervention to focus on the sample 12 manually. As focusing mechanism requires smooth movement, the actuatorl8 (which can be a stepper motor] with micro stepping technique, is a low-cost effective solution for the above-mentioned applications, when compared to a piezo system or the conventional system available in the present market.

[0023] It should be understood that embodiments explained in the description above are only illustrative and do not limit the scope of this invention. Many such embodiments and other modifications and changes in the embodiment explained in the description are envisaged. The scope of the invention is only limited by the scope of the claims

Claims

We Claim:

1. A control unit (10] for focusing a sample (12], said control unit (10] adapted to : identify multiple zones (14] to focus in said sample (12]; control a movement of an objective lens (16] over at least one zone (14(a]] of said sample (14] in a predefined distance range from said sample (12]; detect a focused point within said predefined distance range corresponding to said at least one focused zone (14 (a]] of said sample (12] ; determine a new distance range to focus said objective lens (16] over at least one next zone (14 (b]] of said sample (12], from said detected focused point; detect a new focused point within said new distance range corresponding to said at least one next zone (14 (b]] of said sample (12]

2. The control unit (10] as claimed in claim 1, wherein said detected focused point of said at least one focused zone (14(a]] is identified as an average point for said at least one next focused zone (14(b]] of said sample (12].

3. The control unit (10] as claimed in claim 2, wherein said new distance range is calculated by adding a predefined value to said identified average point

4. The control unit (10] as claimed in claim 1, wherein said control unit (10] adapted to control said movement of said objective lens (16] over said sample (12] by controlling an actuator (18] connected to said objective lens (16].

5. A focusing system (11] comprising : a sample holder (13] to hold a sample (12]; an objective lens (16] positioned above said sample holder (13]; an actuator (18] connected to said objective lens (16], and adapted to adjust said objective lens (16] over said sample (12]; a control unit (10] electronically connected to said actuator (18]; characterized in that : said control unit (10] adapted to: identify multiple zones (14] in said sample (12]; control a movement of said objective lens (16] over at least one zone (14(a]] of said sample (14] in a predefined distance range from said sample (12]; detect a focused point within said predefined distance range corresponding to said at least one focused zone (14(a]] of said sample (12] ; determine a new distance range to focus said objective lens (16] over at least one next zone (14 (b]] of said sample (12], from said detected focused point; detect a new focused point within said new distance range corresponding to said at least one next zone (14(b]] of said sample (12]

6. The focusing system (13] as claimed in claim 5, is chosen from a group comprising a microscopic system, a semi-conductor chip designing system, an optical fiber designing system and the like.

7. The focusing system (13] as claimed in claim 5, comprises a first motor assembly (20] and a second motor assembly (22] connected to said sample holder (13] to adjust said sample holder (13] in x-axis and y-axis direction respectively.

8. A method of focusing on a sample (12], said method comprising: identifying multiple zones (14] in said sample (12]; controlling a movement of an objective lens (16] over at least one zone (14(a]] of said sample (12] in a predefined distance range from said sample (12]; detecting a focused point within said predefined distance range corresponding to said at least one focused zone (14 (b]] of said sample (12]; determining a new distance range to focus said objective lens (16] over at least one next zone (14(b]] of said sample (12], from said detected focused point; detecting a new focused point within said new distance range corresponding to said at least one next zone (14(b]] of said sample (12]

9. The method as claimed in claim 8, wherein moving said objective lens (16] over said sample (12] comprises focusing at least one zone (14] at a time.

10. The method as claimed in claim 8, wherein said detected focused point of at least one zone (14(a]] is identified as an average point for next focused zone (14(b]] of said sample (12]

Dated this 29th day of November, 2019 (Digitally signed]

Siddharth Karkhanis

On-behalf of the Applicants (IN /PA- 1195]