CN218974377U

CN218974377U - Embryo peripheral liquid detection system

Info

Publication number: CN218974377U
Application number: CN202220646084.6U
Authority: CN
Inventors: 徐艇; 郭正飞
Original assignee: Wuxi Ruisi Medical Technology Co ltd
Current assignee: Wuxi Ruisi Medical Technology Co ltd
Priority date: 2022-03-24
Filing date: 2022-03-24
Publication date: 2023-05-05
Anticipated expiration: 2032-03-24

Abstract

The utility model discloses an embryo peripheral liquid detection system, which comprises a shell, wherein an objective table for placing an embryo cuvette, a probe mechanism for detecting the embryo peripheral liquid in the embryo cuvette and an imaging device for collecting image information of the embryo cuvette are arranged in the shell, an analysis and control device for analyzing the embryo peripheral liquid and controlling the operation of the probe mechanism is arranged outside the shell, the input end of the analysis and control device is connected with the output end of the imaging device, and the output end of the analysis and control device is connected with the controlled end of the probe mechanism. The utility model not only can realize embryo culture, but also can detect metabolites or secreted proteins in peripheral fluid in real time, solves the limitation of traditional embryo morphological embryo quality evaluation, and improves the reliability of embryo quality evaluation.

Description

Embryo peripheral liquid detection system

Technical Field

The utility model relates to the technical field of embryo detection, in particular to an embryo peripheral fluid detection system.

Background

Embryo quality is one of the key factors for success of pregnancy, and the developmental potential of embryos, i.e., the assessment of embryo quality, directly affects the screening of transferred embryos and the outcome of pregnancy.

At present, the evaluation of embryo quality is mainly performed by a traditional morphological method, namely, according to the rule of embryo fertilization and division, embryo morphology is observed at specific time points, the embryo quality is evaluated and classified by taking morphology as a standard, and the embryo with the highest grade is selected for transplantation. However, the morphological detection has great limitation, relies on subjective judgment of observers, and has no accurate and objective evaluation standard; and so-called morphological quality embryos, there is also a phenomenon of gestation failure after transplantation, which is disadvantageous in obtaining a better gestation outcome. Because of this uncertainty, many assisted reproductive units are within policy tolerances, increasing the number of single transferred embryos, i.e. placing 2 or even more embryos during one transfer to increase pregnancy rate, with a direct consequence of multiple gestations, with event occurrence up to 30% and a serious risk to both the mother and fetus. Single embryo transfer should therefore be encouraged or limited from a safety, ethical, etc. point of view, whereas the key to this technique is an accurate assessment of embryo quality.

The limitations of morphological evaluation of embryo quality are: 1) The significance of morphological indexes is often limited to the surface layer, and the quality of embryo is not a direct causal relationship; 2) The morphological description is influenced by subjective judgment of an evaluator, and unreliable evaluation can be caused by insufficient experience of the practitioner; 3) The classification and definition criteria of morphological indexes are not perfect, for example, abnormal morphological changes of embryos at different development stages are not enough resolution, and a great deal of statistical research is still needed.

For the above reasons, in order to evaluate the quality of an embryo more reliably, it should not be limited to morphological evaluation of an embryo. The existing technical proposal comprises genetic evaluation of embryo, utilizing embryo Preimplantation Genetic Diagnosis (PGD) technology, extracting blastomeres or trophoblasts of embryo for genetic analysis to find abnormal embryo chromosomes and genes, and the examination is more significant for patients with familial genetic diseases; but the effect of mechanical sampling on the subsequent development of the embryo is unknown.

Metabonomics and proteomics are subjects which develop rapidly in cell biology, metabolic pathways and protein expression of embryo development can also show different characteristics in different development stages, and reflect the development potential and metabolic capacity of embryos, and the metabolites and secreted proteins of the embryos are contained in the peripheral liquid of the embryos, so that a new idea can be provided for evaluating the quality of the embryos by detecting the conditions of the metabolites and the secreted proteins of the embryos in the peripheral liquid of the embryos.

Disclosure of Invention

The utility model aims to solve the technical problem of providing an embryo peripheral liquid detection system which not only can realize embryo culture, but also can detect metabolites or secreted proteins in peripheral liquid in real time, and can evaluate embryo quality under the condition of ensuring no influence on embryos.

In order to solve the technical problems, the technical scheme adopted by the utility model is as follows.

The embryo peripheral liquid detection system comprises a shell, wherein an objective table for placing an embryo cuvette, a probe mechanism for detecting the embryo peripheral liquid in the embryo cuvette and an imaging device for collecting image information of the embryo cuvette are arranged in the shell, an analysis and control device for analyzing the embryo peripheral liquid and controlling the operation of the probe mechanism is arranged outside the shell, the input end of the analysis and control device is connected with the output end of the imaging device, and the output end of the analysis and control device is connected with the controlled end of the probe mechanism.

Above-mentioned embryo periphery liquid detecting system, the through-hole has been seted up at the middle part of objective table, and the embryo cuvette is placed on the objective table, imaging device is located the below of through-hole.

According to the embryo peripheral liquid detection system, the inner cavity is divided into the left part and the right part by the shell through the partition board, the objective table and the imaging device are arranged in the left cavity, and the probe mechanism is arranged in the right cavity; a heating plate is arranged at the top of the shell corresponding to the left cavity, and a lighting lamp is arranged at the top of the shell right above the corresponding through hole; the left cavity is internally provided with a humidifying device, a gas control device and a hygrothermograph, wherein the output end of the hygrothermograph is connected with the input end of the analysis and control device, and the output end of the analysis and control device is respectively connected with the controlled ends of the heating plate, the illuminating lamp, the humidifying device and the gas control device.

The probe mechanism comprises a stepping motor fixedly arranged in the cavity on the right side of the shell, the controlled end of the stepping motor is connected with the output end of the analysis and control device, the output end of the stepping motor is provided with a miniature probe clamp through a fixing device, and a miniature probe for detecting or acquiring the components of the embryo peripheral liquid is clamped in the miniature probe clamp.

Above-mentioned embryo periphery liquid detecting system, the baffle includes upper baffle and the lower baffle of relative setting from top to bottom, and the rotatory baffle of being convenient for form miniature probe and pass the passageway is installed in the rotation between upper baffle and the lower baffle.

By adopting the technical scheme, the utility model has the following technical progress.

The utility model not only can realize the culture of the embryo, but also can detect the metabolite or secreted protein in the peripheral fluid, solves the limitation of the traditional embryo morphological embryo quality evaluation, can scientifically evaluate the embryo quality under the condition of ensuring no influence on the embryo, and improves the reliability of embryo quality evaluation; the following advantages are particularly present.

1) The subjective factors are small, and the deviation generated by artificial subjective factors only depending on embryo morphology observation is reduced; 2) The noninvasive sampling can not cause mechanical damage to the embryo, and the operation of a closed box body reduces the influence on the embryo development caused by the changes of external temperature, humidity, illumination and the like in the embryo inspection process; 3) Real-time detection, which can detect the peripheral liquid of the embryo at a specific embryo development time node, and is beneficial to the discovery of key events of embryo development; 4) The embryology inspection method is enriched, a tool is provided for analyzing metabolites or secreted proteins in the embryo peripheral fluid, and more accurate embryo quality assessment is facilitated.

Drawings

FIG. 1 is a schematic diagram of the structure of the present utility model;

wherein: 1. the device comprises a shell, 2, a heating plate, 3, an illuminating lamp, 4, a humidifying device, 5, a gas control device, 6, an upper partition plate, 7, a rotary partition plate, 8, a lower partition plate, 9, an objective table 10, an embryo cuvette, 11, a hygrothermograph, 12, an imaging device, 13, a microprobe, 14, a microprobe clamp, 15, a fixing device, 16, a stepping motor, 17 and an analysis and control device.

Detailed Description

The utility model will be described in further detail with reference to the drawings and the detailed description.

An embryo peripheral liquid detection system has a structure shown in figure 1, and comprises a shell 1, wherein a stage 9, an imaging device 12 and a probe mechanism are arranged in the shell, and an analysis and control device 17 is arranged outside the shell; the object stage 9 is used for placing embryo cuvettes 10; the probe mechanism is used for positioning the miniature probe 13 to the embryo peripheral fluid in the embryo cuvette 10 and detecting or acquiring components of the embryo peripheral fluid; the imaging device 12 is used for collecting image information in the embryo cuvette 10 and positioning embryo development condition and probe mechanism position in the visual field; the input end of the analysis and control device 17 is connected with the output end of the imaging device 12, and the output end of the analysis and control device 17 is connected with the controlled end of the probe mechanism and is used for controlling the probe mechanism to perform probe positioning according to the information acquired by the imaging device 12 and performing optical analysis, electrochemical analysis or component acquisition on the peripheral liquid of the embryo.

The middle part of the objective table 9 is provided with a through hole, the embryo cuvette 10 is placed on the objective table in a mode of covering the through hole, and the imaging device 12 is positioned right below the through hole.

The inner cavity of the shell is divided into a left part and a right part through the partition plate, the partition plate comprises an upper partition plate 6 and a lower partition plate 8 which are arranged up and down oppositely, and a rotary partition plate 7 is installed between the upper partition plate 6 and the lower partition plate 8 in a rotating mode. The stage 9 and the imaging device 12 are both disposed in the left-side cavity, and the probe mechanism is disposed in the right-side cavity.

In the embryo culturing process, the rotary baffle 7, the upper baffle 6 and the lower baffle 8 are in a fitting and sealing state so as to separate the spaces at two sides of the shell 1; in the embryo peripheral fluid detection process, the rotary baffle 7, the upper baffle 6 and the lower baffle 8 are in an open state, and at the moment, the probe mechanism can position the miniature probe 13 to the embryo peripheral fluid in the embryo cuvette 10 to detect or acquire the embryo peripheral fluid components.

The probe mechanism comprises a stepping motor 16 fixedly arranged in a cavity on the right side of the shell, a controlled end of the stepping motor is connected with an output end of an analysis and control device 17, a miniature probe clamp 16 is arranged at the output end of the stepping motor through a fixing device 5, and a miniature probe 13 for detecting or acquiring the components of the peripheral liquid of the embryo is clamped in the miniature probe clamp 16. The stepping motor can drive the micro probe 13 to reach the embryo cuvette under the control of the analysis and control device 17 to realize the detection of the embryo peripheral fluid.

In the present utility model, the imaging device 12 may be a phase contrast imaging device to clearly display the embryo morphology; the micro probe 13 can be matched with an electrical micro probe, the diameter of the tip is 1-20 mu m, and the probe is used for the response detection of electroactive metabolites through electrochemical sensing, so that the real-time performance is high; optionally matching an optical micro probe, wherein the diameter of the tip is 1-20 mu m, and the probe is used for sensing response of protein substances; optionally a hollow micro probe with the tip diameter of 1-20 mu m is used for extracting the peripheral liquid of the embryo. The movement precision of the stepping motor 16 is 50nm, and the XYZ three axes are controllable and are used for accurately positioning the miniature probe 13 to the embryo peripheral fluid.

The heating plate 2 is arranged at the top of the shell corresponding to the left cavity and used for controlling the temperature in the cavity, and the illuminating lamp 3 is arranged at the top of the shell corresponding to the position right above the through hole; the left cavity is also internally provided with a humidifying device 4, a gas control device 5 and a hygrothermograph 11, wherein the output end of the hygrothermograph 11 is connected with the input end of an analysis and control device 17, and the output end of the analysis and control device 17 is respectively connected with the controlled ends of the heating plate 2, the illuminating lamp 3, the humidifying device 4 and the gas control device 5, so that the environment state in the cavity can be conveniently regulated in the embryo culture process.

The workflow of the present utility model is as follows.

First, the embryo is cultured: an embryo to be cultured and detected is prepared in an embryo cuvette 10, and the embryo cuvette 10 is placed in a stage 9; the analysis and control device 17 adjusts the embryo culture environment through the heating plate 2, the lighting lamp 3, the humidifying device 4 and the gas control device 5.

Secondly, embryo observation: the embryo cuvette upper cover is uncovered, and the embryo state is observed by the imaging device 12, so that the embryo morphology is clearly displayed in the field of view.

Again, the microprobe is assembled: when detection is needed, the rotary baffle 7 is opened, the rotary baffle 7, the upper baffle 6 and the lower baffle 8 are in an open state, the analysis and control device 17 and the stepping motor 16 are started, and the micro probes 13 of different types are assembled on the micro probe clamp 14 according to different detection targets; the microprobe 13 is moved by the stepper motor 16 to the peripheral fluid near the target embryo without touching the embryo, the tip of the microprobe 13 being clearly shown in the field of view.

Finally, embryo peripheral fluid detection:

when the micro probe 13 is matched with an electrical micro probe, the electrical micro probe is directly connected with the analysis and control device 17 through a data line and is used for detecting the electroactive metabolites released by the embryo in real time, the electroactive metabolites are sensed by the electrical detection probe and are transmitted to the analysis and control device, and the analysis and control device 17 judges whether the metabolites in the peripheral fluid of the embryo are abnormal or not through the height of the electrical signal.

When an optical microprobe is selected for detecting secreted proteins released by an embryo, the tip of the microprobe is modified with a capture antibody capable of specifically binding with the secreted proteins, then the probe is incubated in the peripheral liquid of the embryo for 20-30 min, the secreted proteins are bound to the tip of the microprobe, the microprobe 13 is moved out of the peripheral liquid of the embryo by a stepping motor 16, the microprobe 13 is taken out of the shell 1, the tip of the microprobe 13 is washed by PBS buffer, then incubated with a fluorescent marker detection antibody and washed, the fluorescent marker detection antibody can be specifically bound with the secreted proteins, fluorescent signal detection is carried out in the analysis and control device 17, and whether the secreted proteins in the peripheral liquid of the embryo are abnormal or not is judged according to the intensity of the fluorescent signal.

When the hollow microprobe is selected, the hollow microprobe is used for extracting the peripheral liquid of the embryo, the peripheral liquid of the embryo is extracted into the hollow microprobe by using the analysis and control device 17 after the hollow microprobe is moved to the peripheral liquid of the target embryo by the stepping motor 16, and the peripheral liquid in the hollow microprobe can be subjected to metabolite analysis such as mass spectrometry analysis and the like by means of other platforms.

According to the utility model, the miniature probe is arranged and is penetrated into peripheral fluid near the embryo by the stepping motor, so that metabolites or secreted proteins in the peripheral fluid are detected, and mechanical damage to the embryo is avoided; the detection process is in a sealed and culturable environment, so that the influence of the external environment on embryo development in the detection process is reduced; the detection has real-time performance, and is favorable for finding critical events of embryo development.

The application of the utility model provides a method for detecting metabolites and secreted proteins of embryos, solves the limitation that embryo quality evaluation is carried out only by relying on embryo morphology in the prior art, and improves the reliability of embryo quality evaluation.

Claims

1. Embryo peripheral fluid detecting system, its characterized in that: the device comprises an object stage (9) for placing an embryo cuvette (10), a probe mechanism for detecting the peripheral liquid of the embryo in the embryo cuvette (10) and an imaging device (12) for collecting the image information of the embryo cuvette (10), wherein the peripheral liquid of the embryo is analyzed and an analysis and control device (17) capable of controlling the operation of the probe mechanism is arranged, the input end of the analysis and control device (17) is connected with the output end of the imaging device (12), and the output end of the analysis and control device (17) is connected with the controlled end of the probe mechanism.

2. The embryo peripheral fluid detection system, as set forth in claim 1, wherein: through holes are formed in the middle of the objective table (9), the embryo cuvettes (10) are placed on the objective table, and the imaging device (12) is located below the through holes.

3. The embryo peripheral fluid detection system, as set forth in claim 2, wherein: be provided with heating plate (2), light (3), humidification device (4), gas control device (5) and hygrothermograph (11) in the cavity of placing embryo cuvette, wherein the input of analysis and controlling means (17) is connected to the output of hygrothermograph (11), and the controlled end of heating plate (2), light (3), humidification device (4), gas control device (5) is connected respectively to the output of analysis and controlling means (17).

4. The embryo peripheral fluid detection system, as set forth in claim 3, wherein: the probe mechanism comprises a stepping motor (16) fixedly arranged on one side of the embryo cuvette, a controlled end of the stepping motor is connected with an output end of the analysis and control device (17), a miniature probe clamp (14) is arranged at the output end of the stepping motor through a fixing device (15), and a miniature probe (13) for detecting the components of the peripheral liquid of the embryo is clamped in the miniature probe clamp (14).

5. The embryo peripheral fluid detection system, as set forth in claim 4, wherein: a rotary baffle (7) which is convenient for forming a micro probe (13) to pass through the channel is arranged between the embryo cuvette and the stepping motor.