Intelligent acoustofluidics enabled mini-bioreactors for human brain organoids.
Intelligent acoustofluidics enabled mini-bioreactors for human brain organoids.
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智能声流体使人类大脑类器官的微型生物反应器成为可能。
DOI：
10.1039/d1lc00145k
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发表时间：
2021-06-01
期刊：
影响因子：
6.1
通讯作者：
Guo F
中科院分区：
文献类型：
--
作者：
Cai H;Ao Z;Wu Z;Song S;Mackie K;Guo F
声流控技术结合声学和微流控技术，提供了一种独特的手段来操纵细胞和液体，在生物医学科学和转化医学中有着广泛的应用。然而，它是具有挑战性的标准化和保持目前的声流控设备和系统的优良性能，由于多种因素，包括设备到设备的变化，手动操作，环境因素，样品的变异性等，在这里，为了解决这些挑战，我们提出了“智能声流控”-一个自动化系统，涉及声流控设备设计，传感器融合，智能控制器集成。作为概念验证，我们开发了用于人脑类器官培养的基于智能声流控的微型生物反应器。我们的微型生物反应器由三个组件组成：（1）通过声学螺旋相位涡方法进行无接触旋转操作的转子，（2）用于实时跟踪旋转动作的摄像头，以及（3）用于旋转操作闭环调节的基于强化学习的控制器。在仿真和实验环境中训练基于强化学习的控制器后，我们的微型生物反应器可以实现孔板中转子的自动旋转。重要的是，我们的微型生物反应器可以对转子的旋转模式、方向和速度进行出色的控制，而不受转子重量、液体体积和操作温度的波动影响。此外，我们证明了我们的微型生物反应器可以在长期培养期间稳定地保持脑类器官的旋转速度，并增强脑类器官的神经分化和均匀性。与现有的声流控技术相比，该智能系统在自动化程度、鲁棒性和准确性等方面具有上级性能，在生物电子学和微流控实验领域具有广阔的应用前景。
Acoustofluidics, by combining acoustics and microfluidics provides a unique means to manipulate cells and liquids for broad applications in biomedical sciences and translational medicine. However, it is challenging to standardize and maintain excellent performance of current acoustofluidic devices and systems due to a multiplicity of factors including device-to-device variation, manual operation, environmental factors, sample variability, etc. Herein, to address these challenges, we propose “intelligent acoustofluidics” - an automated system that involves acoustofluidic device design, sensor fusion, and intelligent controller integration. As a proof-of-concept, we developed intelligent acoustofluidics based mini-bioreactors for human brain organoid culture. Our mini-bioreactors consist of three components: (1) rotors for contact-free rotational manipulation via an acoustic spiral phase vortex approach, (2) a camera for real-time tracking of rotational actions, and (3) a reinforcement learning-based controller for closed-loop regulation of rotational manipulation. After training the reinforcement learning-based controller in simulation and experimental environments, our mini-bioreactors can achieve the automated rotation of rotors in well-plates. Importantly, our mini-bioreactors can enable excellent control over rotational mode, direction, and speed of rotors, regardless of fluctuations of rotor weight, liquid volume, and operating temperature. Moreover, we demonstrated our mini-bioreactors can stably maintain the rotational speed of brain organoids during long-term culture, and enhance neural differentiation and uniformity of brain organoids. Comparing with current acoustofluidics, our intelligent system has a superior performance in terms of automation, robustness, and accuracy, highlighting the potential of novel intelligent systems in bioelectronics and microfluidics experimentation.
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