Development and validation of an automated robotic system for preparation of embryo culture dishes

Objective To study the development and clinical validation of the ART Pipetting Robot for the IVF Laboratory (APRIL), a liquid-handling robot customized for the precise preparation of microdroplet culture dishes in the field of in vitro fertilization (IVF). Design A prospective randomized study conducted at an academic IVF center comparing mouse and human embryo outcomes and quantitative measures of accuracy in embryo dishes prepared using APRIL compared with standard manual preparation. Subjects The study involved the assessment of the automated culture dish preparation system, APRIL, compared to manual preparation methods in the context of IVF. Exposure APRIL, an enclosed liquid-handling robot equipped with custom 3D-printed adapters and designed to dispense embryo culture media and mineral oil into microdroplet culture dishes. Main Outcome Measures The study evaluated the precision and consistency of APRIL in culture dish preparation looking at droplet mass, pH of prepared media droplets, and mouse and human embryo development rates. Clinical implementation was assessed by comparing embryo development and outcomes in dishes prepared by APRIL and human embryologists. Results Compared with embryo culture dishes prepared using standard manual procedures, embryo culture dishes prepared using APRIL demonstrated a greater than ten-fold improvement in consistence (CV 0.46% vs. 6-7%), maintained optimal pH levels (pH range 7.281-7.33 vs 7.275-7.311), and had a greater mouse embryo blastocyst rate (100% vs 90-91%). Human embryos cultured in dishes prepared by APRIL had a higher rate of development to Day 3 (92.4% vs. 82.6%, p<0.05) and Day 5 (19.75% vs. 15.57%) and a total number of usable embryos (50.3% vs. 46.1%) compared with manually prepared dishes, though the last two outcomes did not reach statistical significance. Conclusion The results suggest that the use of an automated robotic system for preparation of embryo culture dishes may improve accuracy and outcome measures while reducing the need for trained laboratory personnel to manually prepare the dishes.