System and method for rapid positioning and viewing of embryos in a culture dish

Abstract

Provided is a system for quickly locating and observing embryos in a culture dish, comprising a third-magnification imaging system for imaging a culture dish area at a third magnification and searching for and locating an embryo culture droplet area; a second-magnification imaging system for imaging the embryo culture droplet area at a second magnification and searching for and locating an embryo within the embryo culture droplet area to determine an embryo position; and a first-magnification imaging system for imaging the embryo position at a first magnification to achieve microscopic observation of the embryo; the magnifications of the first-magnification imaging system, the second-magnification imaging system, and the third-magnification imaging system decrease in order. The system can be adapted to a common and inexpensive culture dish, and solves the problem of embryos being unable to be clearly imaged or photographed due to wall-hanging.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of assisted reproduction, and in particular to a system and method for quickly locating and observing embryos in a culture dish. BACKGROUND

[0002] In recent years, the population of assisted reproduction has been increasing, and assisted reproduction technology has been developing and applied more and more rapidly.

[0003] For an assisted reproduction medical institution, a large number of different assisted reproduction populations need to be faced every day, and multiple embryos need to be provided for doctors and users to culture and select, so as to select the optimal embryo for further cultivation. For the tiny embryo invisible to the human eye, it is usually stored in a culture dish provided with multiple embryo culture medium droplets. How to quickly and accurately locate a certain embryo under a microscope and observe its development state is a problem to be solved. In addition, the existing embryo observation system often needs to be matched with a special and expensive culture dish. For users using ordinary culture dishes, the existing embryo observation system is difficult to accurately locate and capture high-definition images of the target embryo.

[0004] Therefore, it is necessary to study a system and method for quickly locating and observing embryos in a culture dish to solve one or more of the above technical problems. SUMMARY

[0005] To solve at least one of the above technical problems, according to an aspect of the present application, a system for quickly locating and observing embryos in a culture dish is provided, characterized in that it comprises:

[0006] a third magnification imaging system for imaging a culture dish area at a third magnification and searching and locating an embryo culture droplet area;

[0007] a second magnification imaging system for imaging the embryo culture droplet area at a second magnification and searching and locating an embryo in the embryo culture droplet area to determine the embryo position; and

[0008] a first magnification imaging system for imaging the embryo position at a first magnification to realize microscopic observation of the embryo;

[0009] The magnifications of the first magnification imaging system, the second magnification imaging system and the third magnification imaging system decrease in turn.

[0010] According to another aspect of the present application, the third magnification imaging system is a low magnification imaging system, the second magnification imaging system is a medium magnification imaging system, and the first magnification imaging system is a high magnification imaging system.

[0011] According to another aspect of the present application, the first magnification imaging system is a twenty-fold imaging system, and the third magnification imaging system is a one-fold imaging system.

[0012] According to another aspect of the present application, the system for quickly locating and observing embryos in a culture dish further comprises a switching mechanism for moving the first magnification imaging system, the second magnification imaging system and the third magnification imaging system to a corresponding imaging position of the embryo culture dish one by one.

[0013] According to another aspect of the present application, the embryo culture dish contains a plurality of spaced embryo culture liquid drops, and embryos are placed in the embryo culture liquid drops, and an oil sealing layer is covered on the embryo culture liquid drops.

[0014] According to another aspect of the present application, the bottom surface of the embryo culture dish for placing embryos is a plane.

[0015] According to another aspect of the present application, the first magnification imaging system, the second magnification imaging system and the third magnification imaging system share a light source.

[0016] According to another aspect of the present application, the first magnification imaging system and the second magnification imaging system use different magnification micro-objectives and share light path elements outside the micro-objectives.

[0017] According to another aspect of the present application, a method for quickly locating and observing embryos in a culture dish using the system described above is provided, and the method comprises the following steps:

[0018] imaging the culture dish region at a third magnification and searching and locating the embryo culture liquid drop region;

[0019] imaging the embryo culture liquid drop region at a second magnification and searching and locating the embryo in the embryo culture liquid drop region to determine the embryo position;

[0020] imaging the embryo position at a first magnification to realize microscopic observation of the embryo;

[0021] wherein the magnifications of the first magnification imaging system, the second magnification imaging system and the third magnification imaging system decrease in turn.

[0022] According to another aspect of the present application, the first magnification imaging system is a twenty-fold imaging system, the second magnification imaging system is a four-fold imaging system, and the third magnification imaging system is a one-fold imaging system.

[0023] The present application can achieve one or more of the following technical effects:

[0024] Compared with moving a high magnification microscope to scan the embryo position in the whole region, by first using a one-fold imaging system to quickly locate the transparent embryo culture liquid drop region, then using a four-fold imaging system to locate the XY position of the embryo, and finally using a twenty-fold imaging system to accurately locate the Z position of the embryo, the scanning area of the high magnification microscope can be greatly reduced, and the locating efficiency can be improved.

[0025] The common flat-bottomed culture dish can be adapted, and the use cost of culture dish consumables is greatly reduced;

[0026] The system can be used for accurately and efficiently observing multiple embryos for assisted reproduction, greatly improving efficiency and saving cost;

[0027] The problem that the embryos cannot be clearly imaged or observed due to being hung on the inclined wall of the special dish is solved;

[0028] The third light source is used for oblique upward incidence, which can accurately and quickly image and position the transparent embryo culture medium droplet covered by the oil sealing layer, solve the imaging difficulty problem of the covered transparent embryo culture medium droplet, and then quickly position the embryo culture medium region. BRIEF DESCRIPTION OF DRAWINGS

[0029] The application will be further described in detail below in combination with the drawings and specific embodiments.

[0030] Figure 1 It is a structural schematic diagram of a system for quickly positioning and observing embryos in a culture dish according to a preferred embodiment of the application.

[0031] Figure 2 It is a structural schematic diagram of a third-magnification imaging system according to a preferred embodiment of the application.

[0032] Figure 3 It is a structural schematic diagram of a system for quickly positioning and observing embryos in a culture dish according to a preferred embodiment of the application. Figure 1

[0033] Figure 4 It is a working schematic diagram of a third-magnification imaging system according to a preferred embodiment of the application.

[0034] Figure 5 It is a schematic diagram of imaging results of an embryo culture dish and the embryo culture medium liquid contained therein by using a third-magnification imaging system according to a preferred embodiment of the application. DETAILED DESCRIPTION

[0035] The best mode of the application will be described below in combination with the drawings and preferred embodiments. The specific embodiments are used to explain the application in detail, and should not be understood as limiting the application. Various modifications and changes can be made without departing from the spirit and essential characteristics of the application, and these should be included in the protection scope of the application.

[0036] Example 1

[0037] According to a preferred embodiment of the application, referring to Figures 1-3 , a system for quickly positioning and observing embryos in a culture dish is provided, which is characterized by comprising: ​

[0038] a third magnification imaging system for imaging the culture dish area at a third magnification and searching and locating the embryo culture droplet area;

[0039] a second magnification imaging system for imaging the embryo culture droplet area at a second magnification and searching and locating the embryo within the embryo culture droplet area to determine the embryo position; and

[0040] a first magnification imaging system for imaging the embryo position at a first magnification to achieve microscopic observation of the embryo;

[0041] The magnifications of the first magnification imaging system, the second magnification imaging system and the third magnification imaging system are sequentially decreased.

[0042] According to still another preferred embodiment of the present application, the third magnification imaging system is a low magnification imaging system, the second magnification imaging system is a medium magnification imaging system, and the first magnification imaging system is a high magnification imaging system.

[0043] According to still another preferred embodiment of the present application, the first magnification imaging system is a twenty magnification imaging system, and the third magnification imaging system is a one magnification imaging system.

[0044] According to still another preferred embodiment of the present application, the system for quickly locating and observing the embryo in the culture dish further comprises a switching mechanism for moving the first magnification imaging system, the second magnification imaging system and the third magnification imaging system to the corresponding shooting positions of the embryo culture dish alternatively.

[0045] According to still another preferred embodiment of the present application, the embryo culture dish contains a plurality of spaced embryo culture droplets, the embryo culture droplets contain embryos, and the embryo culture droplets are covered with an oil sealing layer.

[0046] According to still another preferred embodiment of the present application, the bottom surface of the embryo culture dish for placing the embryo is planar.

[0047] According to still another preferred embodiment of the present application, the first magnification imaging system, the second magnification imaging system and the third magnification imaging system share a light source.

[0048] According to still another preferred embodiment of the present application, the first magnification imaging system and the second magnification imaging system adopt different magnification microscopic objectives and share the light path elements outside the microscopic objectives.

[0049] According to still another preferred embodiment of the present application, a method for quickly locating and observing the embryo in the culture dish by using the aforementioned system is further provided, and the method comprises the following steps:

[0050] imaging the culture dish area at a third magnification and searching and locating the embryo culture droplet area;

[0051] imaging the embryo culture droplet area at a second magnification and searching and locating the embryo within the embryo culture droplet area to determine the embryo position;

[0052] imaging the embryo position at a first magnification to realize microscopic observation of the embryo;

[0053] wherein the magnifications of the first magnification imaging system, the second magnification imaging system and the third magnification imaging system are sequentially decreased.

[0054] According to still another preferred embodiment of the present application, the first magnification imaging system is a twenty-fold magnification imaging system, the second magnification imaging system is a four-fold magnification imaging system, and the third magnification imaging system is a one-fold magnification imaging system.

[0055] According to a preferred embodiment of the present application, referring to Figure 1 , the first magnification imaging system comprises a first light source 30, a first light collecting unit 31, a first microscope objective lens unit 32 and a first camera 33.

[0056] Preferably, the second magnification imaging system comprises a second light source 20, a second light collecting unit 21, a second microscope objective lens unit 22 and a second camera 23.

[0057] Preferably, the third magnification imaging system comprises a third light source 10 and a third camera 11.

[0058] According to still another preferred embodiment of the present application, the third magnification imaging system is a one-fold magnification imaging system, the second magnification imaging system is a four-fold magnification imaging system, and the first magnification imaging system is a twenty-fold magnification imaging system.

[0059] Advantageously, by first using the one-fold magnification imaging system to take a picture of the culture dish placed on the rack 40, quickly locating the transparent embryo culture medium droplet area, then using the four-fold magnification imaging system to locate the XY position and coarsely adjust the Z position of the embryo, and finally using the twenty-fold magnification imaging system to precisely locate the Z position of the embryo, the scanning area of the high magnification microscope can be greatly reduced, and the positioning efficiency is improved.

[0060] According to still another preferred embodiment of the present application, the first magnification imaging system further comprises a first mirror, and the second magnification imaging system further comprises a second mirror. The arrangement of the mirrors is advantageous for making the imaging system layout compact, for example, the first light source and the first light collecting unit are arranged on the top, and the first microscope objective lens unit and the first camera are arranged on the bottom, forming a parallel arrangement structure, which can greatly reduce the space occupation.

[0061] According to still another preferred embodiment of the present application, the switching mechanism is a linear motion mechanism and is used to selectively move the first magnification imaging system, the second magnification imaging system and the third magnification imaging system to the corresponding shooting positions of the embryo culture dish.

[0062] According to another preferred embodiment of the present application, referring to Figure 5 , the embryo culture dish contains a plurality of spaced embryo culture droplets in which embryos are placed, and the embryo culture droplets are covered with an oil sealing layer. Preferably, the bottom surface of the embryo culture dish for placing embryos is planar.

[0063] According to another preferred embodiment of the present application, the oil sealing layer is paraffin oil.

[0064] According to another preferred embodiment of the present application, the first magnification imaging system, the second magnification imaging system and the third magnification imaging system share a light source.

[0065] According to another preferred embodiment of the present application, the first magnification imaging system and the second magnification imaging system share a light source, a condensing unit and a camera, and the switching mechanism is used to switch the first microscope objective unit and the second microscope objective unit to the corresponding shooting positions of the embryo culture dish.

[0066] It can be understood that the low magnification and high magnification imaging systems share a light source, and when different objectives are used, the objectives and the subsequent parts are switched under the light source. The low magnification and high magnification imaging systems share a light source and a tube lens behind the objectives, and when different objectives are used, only the objectives are switched.

[0067] According to another preferred embodiment of the present application, referring to Figure 4 , the working principle of the third magnification imaging system is as follows: the embryo culture dish 3 contains a plurality of transparent embryo culture medium droplets 4 arranged at intervals, a transparent oil sealing layer 5 is contained in the embryo culture dish 3 and covers the transparent embryo culture medium droplets 4, a third light source 10 is arranged to emit light to the transparent oil sealing layer 5 and the transparent embryo culture medium droplets 4 at a first predetermined angle with respect to a first plane in which the embryo culture dish 3 is placed, and a third camera 11 receives the light reflected from the transparent embryo culture medium droplets 4 and images the transparent embryo culture medium droplets 4.

[0068] Preferably, as shown in Figure 4 , the first plane is a horizontal plane. It can be understood that the light forms refracted light when passing through the transparent oil sealing layer 5 and the transparent embryo culture medium droplets 4. The first predetermined angle is an acute angle. Advantageously, the third light source 10 performs direct and diffuse reflection illumination on the transparent object to be observed, and by using the principle that light is refracted at the interface between different media and the approximate spherical droplets, part of the light is incident at a small angle, and optical phenomena occur at the interface between the culture medium and the mineral oil (the oil sealing layer), only the light that penetrates the paraffin oil is parallelly emitted, the light that passes through the paraffin oil→the culture medium→the paraffin oil is deflected, thereby leaving light and shade in the imaging system, so as to achieve the contour observation and positioning of the transparent material.

[0069] The present application can obtain one or more of the following technical effects:

[0070] Compared with the mobile high-power microscope scanning the embryo position in the whole area, by first positioning the transparent embryo culture medium droplet area quickly using a one-time imaging system, then positioning the XY position of the embryo using a four-time imaging system, and finally positioning the Z position of the embryo accurately using a twenty-time imaging system, the scanning area of the high-power microscope can be greatly reduced, and the positioning efficiency can be improved.

[0071] The common flat-bottomed culture dish can be adapted, and the use cost of the culture dish consumables can be greatly reduced.

[0072] The present application can be used for accurately and efficiently observing a plurality of embryos for assisted reproduction, greatly improving the efficiency and saving the cost.

[0073] The problem that the embryo is hung on the inclined wall of the special dish and cannot be clearly imaged or observed is solved.

[0074] The third light source obliquely incident from above can be used to accurately and quickly image and position the transparent embryo culture medium droplet covered by the oil sealing layer, solve the imaging difficulty problem of the covered transparent embryo culture medium droplet, and further quickly position the embryo culture medium area.

[0075] Those skilled in the art should understand that the present application is not limited by the above embodiments, and the above embodiments and descriptions in the specification are only to illustrate the principles of the present application. Without departing from the spirit and scope of the present application, various changes and improvements can be made to the present application, and these changes and improvements all fall within the scope of the present application. The scope of protection of the present application is defined by the appended claims and their equivalents.

Claims

1. A system for rapidly locating and observing embryos in a culture dish, characterized in that... The application comprises: an embryo culture dish with a flat bottom surface and containing a plurality of transparent embryo culture medium droplets arranged in intervals, a transparent oil sealing layer being contained in the embryo culture dish and covering the plurality of transparent embryo culture medium droplets; a third magnification imaging system for imaging the culture dish area at a third magnification and searching and locating the embryo culture droplet area; a second magnification imaging system for imaging the embryo culture droplet area at a second magnification and searching and locating the embryo in the embryo culture droplet area to determine the embryo position; and a first magnification imaging system for imaging the embryo position at a first magnification to realize microscopic observation of the embryo; the magnifications of the first magnification imaging system, the second magnification imaging system and the third magnification imaging system decrease in turn; wherein the first magnification imaging system and the second magnification imaging system adopt micro-objectives with different magnifications, and the third magnification imaging system comprises a light source and a camera, the light source is arranged to successively irradiate light to the transparent oil sealing layer and the transparent embryo culture medium droplets at a first predetermined angle with a first plane on which the embryo culture dish is placed, and the camera receives the light reflected from the transparent embryo culture medium droplets and images the plurality of transparent embryo culture medium droplets, the first plane is a horizontal plane, and the light source is arranged to irradiate light to the transparent embryo culture medium droplets covered by the transparent oil sealing layer from an oblique upper side.

2. The system for rapid positioning and viewing of embryos in a culture dish of claim 1, wherein The third magnification imaging system is a low magnification imaging system, the second magnification imaging system is a medium magnification imaging system, and the first magnification imaging system is a high magnification imaging system.

3. The system for rapid positioning and viewing of embryos in a culture dish of claim 2, wherein The first magnification imaging system is a twenty-fold imaging system, and the third magnification imaging system is a one-fold imaging system.

4. The system for rapid positioning and viewing of embryos in a culture dish according to any one of claims 1-3, wherein The application further comprises a switching mechanism for moving the first magnification imaging system, the second magnification imaging system and the third magnification imaging system to the corresponding shooting positions of the embryo culture dish in turn.

5. The system for rapid positioning and viewing of embryos in a culture dish of claim 3, wherein The embryo is placed in the embryo culture droplet.

6. The system for rapid positioning and viewing of embryos in a culture dish according to any one of claims 1-3, wherein The first magnification imaging system, the second magnification imaging system and the third magnification imaging system share the light source.

7. The system for rapid positioning and viewing of embryos in a culture dish according to any one of claims 1-3, wherein The first magnification imaging system and the second magnification imaging system share the optical path elements other than the micro-objective.

8. A method for rapidly locating and observing embryos in a culture dish using the system according to any one of claims 1-7, characterized in that... The application comprises the following steps: imaging the culture dish area at a third magnification and searching and locating the embryo culture droplet area; imaging the embryo culture droplet area at a second magnification and searching and locating the embryo in the embryo culture droplet area to determine the embryo position; imaging the embryo position at a first magnification to realize microscopic observation of the embryo and imaging the development states of the plurality of assisted reproduction embryos; wherein the magnifications of the first magnification imaging system, the second magnification imaging system and the third magnification imaging system decrease in turn.

9. The method of claim 8, wherein The first magnification imaging system is a twenty-fold imaging system, the first magnification imaging system is a four-fold imaging system, and the third magnification imaging system is a one-fold imaging system.

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