WO2020013794A1 - A quantitative phase imaging system comprising an additional module - Google Patents

A quantitative phase imaging system comprising an additional module Download PDF

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Publication number
WO2020013794A1
WO2020013794A1 PCT/TR2019/050563 TR2019050563W WO2020013794A1 WO 2020013794 A1 WO2020013794 A1 WO 2020013794A1 TR 2019050563 W TR2019050563 W TR 2019050563W WO 2020013794 A1 WO2020013794 A1 WO 2020013794A1
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WO
WIPO (PCT)
Prior art keywords
imaging system
prism
light
sample
module
Prior art date
Application number
PCT/TR2019/050563
Other languages
French (fr)
Inventor
Muhammed Fati̇h TOY
Original Assignee
T.C. Istanbul Medipol Universitesi
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by T.C. Istanbul Medipol Universitesi filed Critical T.C. Istanbul Medipol Universitesi
Publication of WO2020013794A1 publication Critical patent/WO2020013794A1/en

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    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/06—Means for illuminating specimens
    • G02B21/08—Condensers
    • G02B21/14—Condensers affording illumination for phase-contrast observation
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/36—Microscopes arranged for photographic purposes or projection purposes or digital imaging or video purposes including associated control and data processing arrangements
    • G02B21/365—Control or image processing arrangements for digital or video microscopes

Definitions

  • the invention is related to an imaging system which enables quantitative phase imaging by adding a light source and an additional module to a standard light microscope.
  • Quantitative phase imaging is an imaging method which provides direct information regarding the sample shape and refractive index without labeling in microscopic imaging. For samples with the known refractive indices, 3 dimensional topography information is obtained by quantitative phase imaging, and for samples with the known thickness information, the refractive index is obtained again by quantitative phase imaging. Quantitative phase microscopic imaging of cell cultures and tissue sections enables quantitative investigation of morphological structure. The most important advantage of this technique is that the invasive protocols like staining on the sample is not needed. Currently the use of quantitative phase microscopes is limited. The reason for this is that the specially developed quantitative phase microscopes or modules that can be attached to the existing microscopes are complex and expensive.
  • Quantitative phase imaging may be implemented in microscopes using different methods.
  • a specially developed microscope system e.g. Digital holographic microscopes
  • This situation may require a very large investment.
  • solutions in which a module can be added to existing microscopes are also available.
  • Some of these modules may comprise components that necessitate precise alignment or that are expensive such as optical modulators, pinholes and beam splitters.
  • the costs of these approaches may be relatively lower in comparison to the first group, but they still comprise expensive components.
  • optical elements necessitate precise alignment also increases the total volume due to the complexity of the mechanical components used and the extra costs.
  • TIE transport intensity
  • the aim of this invention is to provide an imaging system which enables quantitative phase imaging by adding a light source and an additional module to a light transmission microscope.
  • Another aim of this invention is to provide an imaging system having a module that can be attached to present microscopes.
  • Figure 1 An existing microscope and the schematic view of a module having a light source added to this microscope.
  • Tube lens (F) Tube lens
  • the imaging system (1) subject to the invention comprises;
  • -a microscope (2) having components such as a body (B), sample plane (C), lens (D), objective (E), tube lens (F), mirror (G) and a port (H),
  • -a prism (5) located inside the module (4), where the light received from the sample (A) initially contacts and refracts and which is provided with a first prism surface (5.1), a second prism surface (5.2) and filler material (5.3).
  • the invention comprises a microscope (2), a body (B), a sample plane (C) located on the top part of the body, into which the sample (A) whose quantitative phase imaging shall be carried out is placed, a lens (D) located above the sample plane (C) which ensures that the light is collimated before it reaches the sample, an objective (E) which is located on the body (B), and through which the light, which is passing from the sample plane (C) is received, traverses before entering the body (E), a tube lens (F) through which the light that passes, when passing through the objective when said light is being directed towards the mirror (G) in the body (B), a mirror (G) which changes the direction of the light received from the tube lens (F) and a port (H) which delivers the light that has been redirected and is being transmitted out of the body (E) into the module (4).
  • the light source (3) is located on the top part of the lens (D) which is a part of the microscope (2) and it transmits light to the lens (D).
  • the light source (3) is used to illuminate the sample (A) located on the sample plane (C).
  • the light source (3) is a discrete light source.
  • the light source is a coherent light source.
  • the module (4) is placed at the level of the side surface of the body (B) of the microscope (2) in order for the light that passes through the lens (D), sample plane (C), objective (E), tube lens (F) and mirror (G) elements to be transmitted out of the port (H) section.
  • the module (4) can be produced with low cost as it comprises low number of components such as a prism (5) and a camera (7).
  • the module (4) has a structure that can be attached to any kind of microscope.
  • a tube lens may not be present in the microscope body (B) onto which the module (4) is mounted.
  • a mirror may not be present in the microscope body (B) onto which the module (4) is mounted.
  • the mirror (G) in the microscope body (B) onto which the module (4) is mounted may be looking in different directions.
  • the port (H) on the microscope body (B) onto which the module (4) is mounted may be positioned on different points.
  • the module (4) may comprise an optical path extender such as a rectangular prism or a periscope.
  • This optical path extender equalizes the mean optical paths between the light beams reaching to the camera (7), one propagates without change and the other one refracted by the prism (5).
  • the prism (5) while the prism (5) enables the refraction of a part of the light belonging to the sample (A) from the port (H) of the body (B) due its positioning, it allows the remaining part of the light to be propagated without change, on the image plane (6).
  • the prism (5) enables the light received from light sources (3) having different colors to be propagated in different directions by means of diffraction and refraction on horizontal and vertical planes.
  • the prism (5) can be placed at the same as the image plane (6).
  • the prism (5) is placed before or after the image plane (6).
  • the prism (5) is placed on the image plane (6) such that it covers a region of the field of view.
  • the prism (5) is a wedge prism.
  • the prism (5) is a volumetric diffraction grating.
  • the prism (5) is a surface diffraction grating.
  • the prism (5) is shaped such that the bottom edge of the first prism surface (5.1) and the bottom edge of the second prism surface (5.2) are placed such as to have a certain angle remaining between them.
  • the first prism surface (5.1) of the prism (5) has the ability to refract light.
  • the prism (5) has a triangular section.
  • the first prism surface (5.1) and the second prism surface (5.2) is made of glass slide or a cover glass.
  • first prism surface (5.1) and the second prism surface (5.2) are rectangular prisms.
  • first prism surface (5.1) and the second prism surface (5.2) are polygonal prisms such as pentagonal prisms.
  • the filler material (5.3) is filled into the cavity that has been created due to the angle between the first prism surface (5.1) and the second prism surface (5.2) whose bottom edges have been brought together.
  • the refractive index of the filler material (5.3) is compatible with the glass slide or cover glass.
  • the filler material (5.3) has the ability to seep into narrow spaces by means of capillary force and to fill the desired spaces easily.
  • the filler material (5.3) can maintain the shape of the prism (5) as it can be hardened by being cured by heat, light, pressure, atmospheric gas or humidity.
  • the filler material (5.3) can be light cured transparent resin or polymer material.
  • the filler material (5.3) is cured to have a pattern that enables diffraction, besides the refraction of the light that passes through the prism (5).
  • the filler material (5.3) enables the light that may be received from light sources (3) having different wavelengths to be transmitted in different directions and angles after passing through the prism.
  • the prism (5) can be easily produced without requiring any kind of optical production machine by means of the first prism surface (5.1), the second prism surface (5.2) and filler material (5.3).
  • the prism (5) parameters such as prism dimensions, prism material and angles that change the light refraction, are selected to be compatible with the camera (7).
  • the prism (5) does not need fine alignment during imaging.
  • the image plane (6) is the location where the image of the sample (A) on the sample plane (C) is formed.
  • an image such as an interference pattern is formed on the camera (7), which belongs to the beam section of the light beam of the sample that arrives from the imaging plane (6) without being refracted and the light that is refracted by the prism (5).
  • the camera (7) can be placed at any point where the non refracted light beam and the light beam refracted (propagates at an angle towards the non refracted light beam) by the prism (5) overlap each other for a certain amount.
  • the best position for the camera (7) is the closest distance to the image plane (6) where the non refracted and refracted light beams overlap each other.
  • the image readout unit (8) processes the hologram transferred by the camera (7) with known methods and enables to obtain a complex optical wave information.
  • the complex wave information calculated by the image readout unit (8) and the image of the sample (A) on the sample plane (C) are obtained without using methods such as staining which has damaging effects.
  • the amplitude and the phase information (quantitative phase image) of the sample (A) is obtained by means of the complex wave information calculated by the image readout unit (8).
  • the image readout unit (8) is a computer.
  • light is transmitted onto the sample (A) located on the sample plane (C) from the light source (3) in order to illuminate the sample (A).
  • the light beam transmitted by the light source (3) is collimated by the lens (D).
  • the light that passes through the sample (A) then passes through the objective (E) and reaches the tube lens (F) in the body (B).
  • the light that passes from the tube lens (F) hits the mirror (G) that has been placed onto the base preferably at a 45 degree angle and changes the direction of the light beam that moves vertically down to the base to move in a parallel direction.
  • the directed light beam which reaches the port (H) portion of the microscope (2) enters the additional module.
  • a part of the light beam is refracted by the prism (5) inside the module (4) and the other part moves along the image plane (6) without being refracted as it does not come into contact with the prism (5).
  • the refracted and non refracted light beams overlap each other at some point and a camera (7) is placed on this point.
  • a camera (7) is placed on this point.
  • an interference pattern digital hologram
  • This interference pattern that has been obtained from the camera (7) is calculated by the image readout unit (8) and an image which belongs to the sample (A) is formed. Thereby the amplitude and phase information of the sample (A) can be formed quantitatively.

Abstract

The invention is related to an imaging system (1) which enables quantitative phase imaging by adding a light source and an additional module to a standard light microscope.

Description

A QUANTITATIVE PHASE IMAGING SYSTEM COMPRISING AN
ADDITIONAL MODULE
Technical Field
The invention is related to an imaging system which enables quantitative phase imaging by adding a light source and an additional module to a standard light microscope.
Prior Art
Quantitative phase imaging is an imaging method which provides direct information regarding the sample shape and refractive index without labeling in microscopic imaging. For samples with the known refractive indices, 3 dimensional topography information is obtained by quantitative phase imaging, and for samples with the known thickness information, the refractive index is obtained again by quantitative phase imaging. Quantitative phase microscopic imaging of cell cultures and tissue sections enables quantitative investigation of morphological structure. The most important advantage of this technique is that the invasive protocols like staining on the sample is not needed. Currently the use of quantitative phase microscopes is limited. The reason for this is that the specially developed quantitative phase microscopes or modules that can be attached to the existing microscopes are complex and expensive.
Quantitative phase imaging may be implemented in microscopes using different methods. In the first one of the possible alternatives, a specially developed microscope system (e.g. Digital holographic microscopes) can be used. However, this situation may require a very large investment. Besides this, solutions in which a module can be added to existing microscopes are also available. Some of these modules may comprise components that necessitate precise alignment or that are expensive such as optical modulators, pinholes and beam splitters. The costs of these approaches may be relatively lower in comparison to the first group, but they still comprise expensive components. As some optical elements necessitate precise alignment also increases the total volume due to the complexity of the mechanical components used and the extra costs. It is possible to obtain quantitative phase imaging using a plurality of non focal images without applying any changes to a commercial microscope by means of the transport intensity (TIE) method. However this method has disadvantages as the accuracy of the images obtained with this method is low, and as it cannot be used with motile samples because more than one raw acquisition is required, and it is also affected by vibrations. Due to these reasons, an additional module and an imaging system comprising this module to be used in quantitative phase imaging is required. This module is needed to be simple due to less number of components, low cost, and not requiring precision alignment.
In the Korean patent document numbered KR 101555147 of the prior art, a microscope unit which combines a quantitative phase microscope with a microscope that can examine a sample such as a cell and enables an image which represents the quantitative phase change of each part of a cell to be produced, is disclosed.
In the United States patent document numbered US2013162800 a system and a method which is used to create high contrast quantitative phase images of biological samples is described.
Summary of the invention
The aim of this invention is to provide an imaging system which enables quantitative phase imaging by adding a light source and an additional module to a light transmission microscope.
Another aim of this invention is to provide an imaging system having a module that can be attached to present microscopes.
Another aim of this invention is to provide an imaging system having a low-cost module that has a simple structure which comprises a smaller number of components Detailed Description of Invention
The“Quantitative phase Imaging System Comprising and Additional Module” that has been provided in order to reach the aims of the invention has been illustrated in the attached figures and according to these figures:
Figure 1. An existing microscope and the schematic view of a module having a light source added to this microscope.
Figure 2. The schematic view of the prism used in the module. The parts in the figures have each been numbered and the references of each number have been provided below.
1. Imaging System
2. Microscope
3. Light source
4. Module
5. Prism
5.1 First prism surface
5.2 Second prism surface
5.3 Filler material
6. Image plane 7. Camera
8. Image readout unit
Sample (A)
Body (B)
Sample plane (C)
Lens (D)
Objective (E)
Tube lens (F)
Mirror (G)
Port (H)
The imaging system (1) subject to the invention comprises;
-a microscope (2) having components such as a body (B), sample plane (C), lens (D), objective (E), tube lens (F), mirror (G) and a port (H),
-a light source (3) located at the top section of the microscope (2) which enables to illuminate the sample (A),
-a module (4) where the light beam leaving the microscope (2) is directed towards,
-a prism (5) located inside the module (4), where the light received from the sample (A) initially contacts and refracts and which is provided with a first prism surface (5.1), a second prism surface (5.2) and filler material (5.3).
-an image plane (6) where the sample (A) image is formed inside the module (4), -a camera (7) which enables to acquire an interference pattern obtained by means of the light that is non refracted and refracted by the prism received from the sample (A) inside the module (4),
-an image readout unit (8) into which the images to be read, obtained from the camera (7) are transferred to.
According to an embodiment of the invention, the invention comprises a microscope (2), a body (B), a sample plane (C) located on the top part of the body, into which the sample (A) whose quantitative phase imaging shall be carried out is placed, a lens (D) located above the sample plane (C) which ensures that the light is collimated before it reaches the sample, an objective (E) which is located on the body (B), and through which the light, which is passing from the sample plane (C) is received, traverses before entering the body (E), a tube lens (F) through which the light that passes, when passing through the objective when said light is being directed towards the mirror (G) in the body (B), a mirror (G) which changes the direction of the light received from the tube lens (F) and a port (H) which delivers the light that has been redirected and is being transmitted out of the body (E) into the module (4).
According to an embodiment of the invention, the light source (3) is located on the top part of the lens (D) which is a part of the microscope (2) and it transmits light to the lens (D).
According to an embodiment of the invention the light source (3) is used to illuminate the sample (A) located on the sample plane (C).
In a preferred embodiment of the invention the light source (3) is a discrete light source.
According to another embodiment of the invention the light source is a coherent light source.
According to an embodiment of the invention the module (4) is placed at the level of the side surface of the body (B) of the microscope (2) in order for the light that passes through the lens (D), sample plane (C), objective (E), tube lens (F) and mirror (G) elements to be transmitted out of the port (H) section.
In an embodiment of the invention the module (4) can be produced with low cost as it comprises low number of components such as a prism (5) and a camera (7). According to an embodiment of the invention the module (4) has a structure that can be attached to any kind of microscope.
According to an embodiment of the invention a tube lens may not be present in the microscope body (B) onto which the module (4) is mounted.
According to an embodiment of the invention a mirror may not be present in the microscope body (B) onto which the module (4) is mounted.
According to an embodiment of the invention the mirror (G) in the microscope body (B) onto which the module (4) is mounted may be looking in different directions.
According to another embodiment of the invention the port (H) on the microscope body (B) onto which the module (4) is mounted may be positioned on different points.
According to an embodiment of the invention, the module (4) may comprise an optical path extender such as a rectangular prism or a periscope. This optical path extender equalizes the mean optical paths between the light beams reaching to the camera (7), one propagates without change and the other one refracted by the prism (5).
According to an embodiment of the invention, while the prism (5) enables the refraction of a part of the light belonging to the sample (A) from the port (H) of the body (B) due its positioning, it allows the remaining part of the light to be propagated without change, on the image plane (6).
According to an embodiment of the invention the prism (5) enables the light received from light sources (3) having different colors to be propagated in different directions by means of diffraction and refraction on horizontal and vertical planes.
In a preferred embodiment of the invention the prism (5) can be placed at the same as the image plane (6).
In another embodiment of the invention the prism (5) is placed before or after the image plane (6).
According to an embodiment of the invention the prism (5) is placed on the image plane (6) such that it covers a region of the field of view.
According to an embodiment of the invention the prism (5) is a wedge prism.
According to another embodiment of the invention, the prism (5) is a volumetric diffraction grating.
According to another embodiment of the invention, the prism (5) is a surface diffraction grating.
According to an embodiment of the invention the prism (5) is shaped such that the bottom edge of the first prism surface (5.1) and the bottom edge of the second prism surface (5.2) are placed such as to have a certain angle remaining between them.
According to an embodiment of the invention the first prism surface (5.1) of the prism (5) has the ability to refract light.
In a preferred embodiment of the invention the prism (5) has a triangular section. In a preferred embodiment of the invention the first prism surface (5.1) and the second prism surface (5.2) is made of glass slide or a cover glass.
In a preferred embodiment of the invention the first prism surface (5.1) and the second prism surface (5.2) are rectangular prisms.
In a another embodiment of the invention the first prism surface (5.1) and the second prism surface (5.2) are polygonal prisms such as pentagonal prisms.
According to an embodiment of the invention the filler material (5.3) is filled into the cavity that has been created due to the angle between the first prism surface (5.1) and the second prism surface (5.2) whose bottom edges have been brought together.
According to an embodiment of the invention the refractive index of the filler material (5.3) is compatible with the glass slide or cover glass.
According to an embodiment of the invention the filler material (5.3) has the ability to seep into narrow spaces by means of capillary force and to fill the desired spaces easily.
According to an embodiment of the invention the filler material (5.3) can maintain the shape of the prism (5) as it can be hardened by being cured by heat, light, pressure, atmospheric gas or humidity.
According to an embodiment of the invention the filler material (5.3) can be light cured transparent resin or polymer material.
According to an embodiment of the invention the filler material (5.3) is cured to have a pattern that enables diffraction, besides the refraction of the light that passes through the prism (5). According to an embodiment of the invention the filler material (5.3) enables the light that may be received from light sources (3) having different wavelengths to be transmitted in different directions and angles after passing through the prism.
According to an embodiment of the invention the prism (5) can be easily produced without requiring any kind of optical production machine by means of the first prism surface (5.1), the second prism surface (5.2) and filler material (5.3).
According to an embodiment of the invention the prism (5) parameters such as prism dimensions, prism material and angles that change the light refraction, are selected to be compatible with the camera (7).
According to an embodiment of the invention the prism (5) does not need fine alignment during imaging.
According to an embodiment of the invention the image plane (6) is the location where the image of the sample (A) on the sample plane (C) is formed.
According to an embodiment of the invention an image such as an interference pattern (digital hologram) is formed on the camera (7), which belongs to the beam section of the light beam of the sample that arrives from the imaging plane (6) without being refracted and the light that is refracted by the prism (5).
According to a preferred embodiment of the invention the camera (7) can be placed at any point where the non refracted light beam and the light beam refracted (propagates at an angle towards the non refracted light beam) by the prism (5) overlap each other for a certain amount. According to a preferred embodiment the best position for the camera (7) is the closest distance to the image plane (6) where the non refracted and refracted light beams overlap each other.
According to a preferred embodiment the image readout unit (8) processes the hologram transferred by the camera (7) with known methods and enables to obtain a complex optical wave information.
According to a preferred embodiment the complex wave information calculated by the image readout unit (8) and the image of the sample (A) on the sample plane (C) are obtained without using methods such as staining which has damaging effects.
According to a preferred embodiment, the amplitude and the phase information (quantitative phase image) of the sample (A) is obtained by means of the complex wave information calculated by the image readout unit (8).
According to a preferred embodiment the image readout unit (8) is a computer.
According to an embodiment of the invention light is transmitted onto the sample (A) located on the sample plane (C) from the light source (3) in order to illuminate the sample (A). The light beam transmitted by the light source (3) is collimated by the lens (D). The light that passes through the sample (A) then passes through the objective (E) and reaches the tube lens (F) in the body (B). The light that passes from the tube lens (F) hits the mirror (G) that has been placed onto the base preferably at a 45 degree angle and changes the direction of the light beam that moves vertically down to the base to move in a parallel direction. The directed light beam which reaches the port (H) portion of the microscope (2) enters the additional module. A part of the light beam is refracted by the prism (5) inside the module (4) and the other part moves along the image plane (6) without being refracted as it does not come into contact with the prism (5). The refracted and non refracted light beams overlap each other at some point and a camera (7) is placed on this point. By means of the camera (7), which has been placed, an interference pattern (digital hologram) belonging to the sample (A) is obtained. This interference pattern that has been obtained from the camera (7) is calculated by the image readout unit (8) and an image which belongs to the sample (A) is formed. Thereby the amplitude and phase information of the sample (A) can be formed quantitatively.
Several embodiments can be developed for the imaging system (1) subject to the invention within the scope of these basic concepts and the invention is principally as defined in the claims and therefore it cannot be limited to the examples provided herein.

Claims

1. An imaging system (1) characterized by a microscope (2) having components such as a body (B), sample plane (C), lens (D), objective (E), tube lens (F), mirror (G) and a port (H),
-a light source (3) located at the top section of the microscope (2) which enables to illuminate the sample (A),
-a module (4) where the light beam departing from the microscope (2) is transmitted to,
-a prism (5) located inside the module (4), where the light received from the sample (A) initially contacts and refracts and which is provided with a first prism surface (5.1), a second prism surface (5.2) and filler material (5.3).
-an image plane (6) where the sample (A) image is formed inside the module (4),
-a camera (7) which enables to receive an interference pattern obtained by means of the light that is non refracted and refracted by the prism received from the sample (A) inside the module (4), and
-an image reading unit (8) into which the images to be read, obtained from the camera (7) are transferred to.
2. An imaging system according to claim 1, characterized by comprising a microscope (2), a body (B), a sample plane (C) located on the top part of the body, into which the sample (A) whose quantitative phase imaging shall be carried out is placed, a lens (D) located above sample plane (C) which ensures that the light is collimated before it reaches the sample, an objective (E) which is located on the body (B), and through which the light passes before entering the body (E) that is passing from the sample plane (C) is received, a tube lens (F) through which the light that passes, when passing through the objective when said light is being transmitted to the mirror (G) in the body (B), a mirror (G) which reflects the light received from the tube lens (F) and a port (H) which transmits the light that has been reflected and is being transmitted out of the body (E) into the module (4).
3. An imaging system (1) according to claim 1 or 2 characterized by a light source (3) that is located above the lens (D) which is a part of the microscope (2) and which transmits light to the lens (D).
4. An imaging system (1) according to any of the preceding claims characterized by a light source (3) that is used to illuminate the sample (A) located on the sample plane (C).
5. An imaging system (1) according to any of the preceding claims characterized by a light source (3) that is a discrete light source.
6. An imaging system (1) according to any of the claims 1 to 4, characterized by a light source (3) that is a coherent light source.
7. An imaging system (1) according to any of the preceding claims characterized by a module (4) that is placed at the level of the side surface of the body (B) of the microscope (2) in order for the light that passes through the lens (D), sample plane (C), objective (E), tube lens (F) and mirror (G) elements to be transmitted out of the port (H) section.
8. An imaging system (1) according to any of the preceding claims characterized by a module (4) that can be produced with low cost as it comprises small number of components such as a prism (5) and a camera
(7).
9. An imaging system (1) according to any of the preceding claims characterized by a module (4) that has a compatible structure which can be attached to any kind of microscope.
10. An imaging system (1) according to any of the preceding claims characterized by a module (4) that does not have a tube lens (F) in the microscope body (B) it has been attached to.
11. An imaging system (1) according to any of the preceding claims characterized by a module (4) that does not have a mirror in the microscope body (B) it has been attached to.
12. An imaging system (1) according to any of the preceding claims characterized by a module (4) attached to the microscope body (B) such that the mirror (G) is allowed to look in different directions.
13. An imaging system (1) according to any of the preceding claims characterized by a module (4) attached the microscope body (B) such that it allows the port (H) to be positioned on different points.
14. An imaging system (1) according to any of the preceding claims characterized by a module (4) that comprises an optical path extender such as a rectangular prism or periscope which equalizes the average optical path distances between the light propagating without any change and the light refracted by the prism (5) to reach the camera (7).
15. An imaging system (1) according to any of the preceding claims characterized by a prism (5) that enables the refraction of a part of the light belonging to the sample (A) from the port (H) of the body (B) due its positioning, and allows the remaining part of the light to be transmitted without change, along the image plane (6).
16. An imaging system (1) according to any of the preceding claims characterized by a prism (5) that enables the light received from light sources (3) having different colors to be transmitted in different directions by means of diffraction and refraction on horizontal and vertical planes.
17. An imaging system (1) according to any of the preceding claims characterized by a prism (5) which aligned to be on the image plane (6).
18. An imaging system (1) according to any of the claims 1 to 16, characterized by a prism (5) that is placed before or after the image plane (6).
19. An imaging system (1) according to any of the preceding claims characterized by a prism (5) that is placed on the imaging plane (6) such that it covers a region of the field of view.
20. An imaging system (1) according to any of the preceding claims characterized by a prism (5) which can be a wedge prism.
21. An imaging system (1) according to any of the claims 1 to 19 characterized by a prism (5) which can be a volumetric diffraction grating.
22. An imaging system (1) according to any of the claims 1 to 19 characterized by a prism (5) which can be a surface diffraction grating.
23. An imaging system (1) according to any of the preceding claims characterized by a prism (5) which is shaped such that the bottom edge of the first prism surface (5.1) that has been placed vertical to the ground and the bottom edge of the second prism surface (5.2) are placed such as to have a certain angle remaining between them.
24. An imaging system (1) according to any of the preceding claims characterized by a prism (5) whose first prism surface (5.1) has the ability to refract light.
25. An imaging system (1) according to any of the preceding claims characterized by a prism (5) that has a triangular section.
26. An imaging system (1) according to any of the preceding claims characterized by the first prism surface (5.1) and the second prism surface (5.2) to be made of a glass slide or cover glass.
27. An imaging system (1) according to any of the preceding claims characterized by the first prism surface (5.1) and the second prism surface (5.2) to be shaped like a rectangular prism.
28. An imaging system (1) according to any of the claims 1 to 26 characterized by the first prism surface (5.1) and the second prism surface (5.2) to be a polygonal prism such as a triangular or pentagonal prism.
29. An imaging system (1) according to any of the preceding claims characterized by a filler material (5.3) that is filled into the cavity that has been created due to the angle between the first prism surface (5.1) and the second prism surface (5.2) whose bottom edges have been brought together.
30. An imaging system (1) according to any of the preceding claims characterized by the refractive index of the filler material (5.3) to be compatible with a glass slide or cover glass.
31. An imaging system (1) according to any of the preceding claims characterized by a filler material (5.3) that has the ability to go into narrow spaces by means of capillary force and to fill the desired spaces easily.
32. An imaging system (1) according to any of the preceding claims characterized by a filler material (5.3) which can maintain the shape of the prism (5) as it can be hardened by being cured with heat, light, pressure, atmospheric gas or humidity.
33. An imaging system (1) according to any of the preceding claims characterized by a filler material (5.3) that is a light cured transparent resin or polymer material.
34. An imaging system (1) according to any of the preceding claims characterized by a filler material (5.3) that is cured to have a pattern that enables diffraction, besides the refraction of the light that passes through the prism (5).
35. An imaging system (1) according to any of the preceding claims characterized by a filler material (5.3) that enables the light that may be received from light sources (3) having different wavelengths to be transmitted in different directions and angles after passing through the prism.
36. An imaging system (1) according to any of the preceding claims characterized by a prism (5) that can be easily produced without requiring any kind of optical production machine by means of the first prism surface (5.1), the second prism surface (5.2) and filler material (5.3).
37. An imaging system (1) according to any of the preceding claims characterized by a prism (5) whose parameters such as prism dimensions, prism material and angles that change the light refraction, are selected to be compatible with the camera (7).
38. An imaging system (1) according to any of the preceding claims characterized by a prism (5) that does not necessitate precise alignment during imaging.
39. An imaging system (1) according to any of the preceding claims characterized by an image plane (6) which is the location on which the image of the sample (A) on the sample plane (C) is formed.
40. An imaging system (1) according to any of the preceding claims characterized by a camera (7) which creates an image in the form of an interference pattern (digital hologram), which belongs to the beam section of the light beam of the sample that arrives from the image plane (6) without being refracted and the light that is refracted by the prism (5).
41. An imaging system (1) according to any of the preceding claims characterized by a camera (7) that is placed at any point where the non refracted light beam and the light beam refracted (propagates at an angle towards the non refracted light beam) by the prism (5) overlap each other for a certain amount.
42. An imaging system (1) according to any of the preceding claims characterized by a camera (7) that is placed at any point where the non refracted light beam (propagates at an angle towards the refracted light beam) and the light beam refracted by the prism (5) overlap each other at a certain point.
43. An imaging system (1) according to any of the preceding claims characterized by a camera (7) whose best position is the closest distance to the image plane (6) where the non refracted and refracted light beams overlap each other.
44. An imaging system (1) according to any of the preceding claims characterized by a readout unit (8) that processes the hologram acquired by the camera (7) with known methods and enables to obtain a complex optical wave information.
45. An imaging system (1) according to any of the preceding claims characterized by readout unit (8) that is used to obtain the image of the sample (A) on the sample plane (C) by means of the complex wave information that has been calculated without using methods like staining that have harmful effects.
46. An imaging system (1) according to any of the preceding claims characterized by a readout unit (8) that enables to reach the amplitude and phase information (quantitative phase imaging) of the sample (A) using the calculated complex wave information.
47. An imaging system (1) according to any of the preceding claims characterized by a readout unit (8) that can be a computer.
PCT/TR2019/050563 2018-07-13 2019-07-11 A quantitative phase imaging system comprising an additional module WO2020013794A1 (en)

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TR2018/10036 2018-07-13

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008292939A (en) * 2007-05-28 2008-12-04 Graduate School For The Creation Of New Photonics Industries Quantitative phase microscope
WO2013086527A1 (en) * 2011-12-09 2013-06-13 Massachusetts Institute Of Technology Systems and methods self-referenced quantitative phase microscopy
US20130162800A1 (en) * 2011-12-22 2013-06-27 General Electric Company Quantitative phase microscopy for label-free high-contrast cell imaging using frequency domain phase shift
KR101555147B1 (en) * 2014-06-24 2015-09-23 한국과학기술원 Common-path quantitative phase imaging unit for generating quantitative phase image

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008292939A (en) * 2007-05-28 2008-12-04 Graduate School For The Creation Of New Photonics Industries Quantitative phase microscope
WO2013086527A1 (en) * 2011-12-09 2013-06-13 Massachusetts Institute Of Technology Systems and methods self-referenced quantitative phase microscopy
US20130162800A1 (en) * 2011-12-22 2013-06-27 General Electric Company Quantitative phase microscopy for label-free high-contrast cell imaging using frequency domain phase shift
KR101555147B1 (en) * 2014-06-24 2015-09-23 한국과학기술원 Common-path quantitative phase imaging unit for generating quantitative phase image

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