Automation and Control of Embryo Trophectoderm Cell Biopsy at the Blastocyst Stage

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blastocyst stage trophectoderm cell biopsy automation control computer vision in vitro fertilization

Application of Automation Technology in Embryo Trophectoderm Cell Biopsy

Academic Background
Embryo biopsy is a crucial step in assisted reproductive technology (In Vitro Fertilization, IVF), especially in Preimplantation Genetic Testing (PGT). Through embryo biopsy, doctors can extract a small number of cells from embryos for genetic analysis to avoid the transmission of genetic diseases and improve the success rate of embryo implantation. However, traditional embryo biopsy relies on manual operations, which have issues such as long operation times, unstable success rates, and high risks of embryo damage. With the advancement of single-cell biology research, the introduction of automation technology has become key to solving these problems. This paper aims to develop an automated system based on computer vision and image feedback control algorithms for performing trophoblast (Trophectoderm, TE) biopsy at the blastocyst stage in mice to enhance the precision and repeatability of biopsies.

Source of the Paper
This paper was co-authored by Ihab Abu Ajamieh, Mohammad Al Saaideh, Mohammad Al Janaideh, and James K. Mills from Birzeit University, Memorial University, University of Guelph, and the University of Toronto, respectively. It was published in the 2025 issue of IEEE Transactions on Biomedical Engineering, detailing the development and validation of an automated embryo biopsy system.

Research Process
The main objective of this study is to achieve full-process operation of embryo trophoblast cell biopsy through automation technology, specifically including steps such as embryo reorientation, zona pellucida (Zona Pellucida, ZP) perforation, trophoblast cell extraction, and separation. Below are the detailed processes of the research:

  1. Embryo Reorientation
    Embryo reorientation is the first step in biopsy, aiming to adjust the embryo to a position suitable for ZP perforation. The study developed a feedback control system based on computer vision that monitors the position and orientation of the embryo in real time using a microscope and high-speed camera. The system uses an image processing algorithm to detect the inner cell mass (Inner Cell Mass, ICM) and calculates the rotation angle of the embryo. By controlling the movement of the microscope stage, the system can precisely adjust the orientation of the embryo. Experimental results show that the system can successfully rotate the embryo to the target position from different starting angles with a 100% success rate.

  2. Automation of ZP Perforation
    After embryo reorientation, the system needs to perform ZP perforation to extract trophoblast cells. The study employed laser perforation technology, estimating the thickness of the ZP using a computer vision algorithm and adjusting laser parameters (such as pulse duration and power) to achieve precise perforation. The system moves the embryo to the laser perforation position via visual feedback control and performs multiple perforations to ensure adequate opening of the ZP. Experiments showed that the system could accurately complete ZP perforation without causing additional damage to the embryo.

  3. Trophoblast Cell Extraction
    After ZP perforation, the trophoblast cells naturally protrude from the perforation site, and the system controls the biopsy micropipette to contact and extract these cells using a micromanipulator. The study developed a vision-guided feedback control system that monitors the position of the cells inside the micropipette in real time and adjusts the movement of the micropipette as needed. Experimental results show that the system can successfully extract the predetermined number of trophoblast cells, significantly shortening the operation time.

  4. Trophoblast Cell Separation
    The extracted trophoblast cells need to be completely separated from the embryo using laser separation technology. The study used multi-pulse lasers to cut the intercellular connections and ensured the precision of the separation process through visual feedback control. Experiments showed that the system could efficiently complete cell separation without causing additional damage to the embryo.

Main Results
1. Embryo Reorientation
Experimental results show that the system can successfully rotate the embryo to the target position from different starting angles with a 100% success rate, and the operation time is significantly shorter than manual operation.

  1. ZP Perforation
    The system can accurately complete ZP perforation without causing additional damage to the embryo. Experimental data shows that the success rate of ZP perforation reaches 100%, and the perforation location is highly consistent with the natural hatching position.

  2. Trophoblast Cell Extraction and Separation
    The system successfully extracted the predetermined number of trophoblast cells, significantly shortening the operation time. The success rate of cell separation also reached 100% without causing additional damage to the embryo.

Conclusion and Significance
This study developed an automated embryo biopsy system based on computer vision and image feedback control algorithms, successfully achieving full-process operation of trophoblast cell biopsy at the blastocyst stage in mice. The system not only improved the precision and repeatability of biopsies but also significantly shortened the operation time, reducing the risk of embryo damage. By utilizing existing laboratory equipment, the system has the advantages of high cost-effectiveness and ease of promotion, providing important support for single-cell biology research and the development of assisted reproductive technology.

Highlights of the Study
1. Full-Process Automation
This study achieved full-process automation of embryo biopsy for the first time, including steps such as embryo reorientation, ZP perforation, trophoblast cell extraction, and separation.

  1. High Precision and Repeatability
    Through computer vision and image feedback control algorithms, the system can precisely control the operation of each step, significantly improving the success rate and repeatability of biopsies.

  2. Low Cost and Easy Promotion
    The system utilizes existing laboratory equipment, eliminating the need to purchase expensive instruments, offering high cost-effectiveness and promotional value.

Other Valuable Information
This study also verified the potential application of the automated system in human embryos. Although the experimental subjects were mouse embryos, due to the similarity in morphological characteristics between human and mouse embryos at the blastocyst stage, the system is expected to be applied to human embryo biopsy in the future, further improving the success rate of assisted reproductive technology.