arXiv:2605.19677cs.LGq-bio.QM2026-05

用AI闭环优化低温微针配方,实现高细胞存活率与低毒性兼顾。

Agentic Discovery of Cryomicroneedle Formulations

论文配图:Agentic Discovery of Cryomicroneedle Formulations
图 1 · 摘自论文原文
  • 结合文献数据与贝叶斯优化,构建可自适应的智能筛选流程。
  • 经10轮实验验证,模型预测准确率提升至R²=0.942,细胞复苏存活率达95.15%。
  • 适合缺乏数据科学背景的实验室快速开展低温制剂研发。

低温微针为活细胞微创皮内递送提供了新途径,但其冷冻保护剂配方需兼顾细胞保护、毒性控制与制造可行性。本文提出一种AI辅助的闭环工作流,整合文献整理、高斯过程代理模型、贝叶斯优化与连续湿实验验证。基于42项研究中的198个间充质干细胞冷冻保存配方,构建包含21个成分特征的数据库,并训练具备不确定性感知能力的文献先验模型。该模型虽捕捉到部分文献数据结构,但前瞻性预测表现不佳,因此通过10轮湿实验迭代修正。经过106次实验观测,模型逐步适应低温微针特异性结果:批次均方误差从41.21降至6.86百分点,后期排名相关性持续为正,累计预测-实测总结的R²达0.942。最优配方实现95.15%复苏存活率,且使用低浓度DMSO、 ectoin、乙二醇及胎牛血清。然而,高存活率并未保证微针结构完整,凸显未来需开展多目标优化。结果表明,智能化计算框架可使数据效率低的配方发现更易被无数据专长的实验室采用。项目代码见https://github.com/baitmeister/ML-for-CryoMN。

原文摘要 · Abstract (English)

Cryomicroneedles offer a route to minimally invasive intradermal delivery of living cells, but their cryogenic formulations must reconcile cell protection with constraints on toxicity and device fabrication. Here we report an AI-assisted, closed-loop workflow for cryomicroneedle cryoprotectant discovery that combines literature curation, Gaussian-process surrogate modelling, Bayesian optimization, and sequential wet-lab validation. A curated dataset of 198 mesenchymal stem-cell cryopreservation formulations from 42 studies was converted into 21 ingredient features and used to train an uncertainty-aware literature prior. This model captured moderate structure in the literature data but failed prospectively, motivating iterative wet-lab correction. Across ten validation iterations and 106 wet-lab observations, the model progressively adapted to cryomicroneedle-specific outcomes: batch RMSE decreased from 41.21 to 6.86 percentage points, later-stage rank correlations became consistently positive, and the cumulative wet-lab predicted-versus-measured summary reached $R^2 = 0.942$. The best validated formulation achieved 95.15\% post-thaw viability with low DMSO, ectoin, ethylene glycol, and fetal bovine serum. However, high viability alone did not ensure intact cryomicroneedle formation, highlighting the need for future multi-objective optimization. These results demonstrate that agent-assisted computational infrastructure can make data-efficient formulation discovery more accessible to labs with minimal data expertise in-house. Project code is available at https://github.com/baitmeister/ML-for-CryoMN.

AI制药低温制剂微针递送贝叶斯优化

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