Since its first appearance in the 1960s, solid support-free liquid-liquid chromatography has played an ever-growing role in the field of natural products research. The use of the two phases of a liquid biphasic system, the mobile and stationary phases, renders the technique highly versatile and adaptable to a wide spectrum of target molecules, from hydrophobic to highly polar small molecules to proteins. Generally considered a niche technique used only for small-scale preparative separations, liquid-liquid chromatography currently lags far behind conventional liquid-solid chromatography and liquid-liquid extraction in process modeling and industrial acceptance. This review aims to expose a broader audience to this high-potential separation technique by presenting the wide variety of available operating modes and solvent systems as well as structured, model-based design approaches. Topics currently offering opportunities for further investigation are also addressed. Expected final online publication date for the Annual Review of Chemical and Biomolecular Engineering, Volume 12 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

中文翻译：

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液相色谱：当前的设计方法和未来的途径。

自1960年代首次出现以来，无固体支持的液-液色谱法在天然产物研究领域中发挥着日益重要的作用。液体双相系统的两个相（流动相和固定相）的使用使该技术具有很高的通用性，并适用于从疏水性到高极性的小分子再到蛋白质的各种目标分子。液-液相色谱法通常被认为是仅用于小规模制备分离的利基技术，目前在过程建模和工业验收方面远远落后于常规的液-固色谱法和液-液萃取。这篇综述旨在通过介绍各种可用的操作模式和溶剂系统以及基于模型的结构化设计方法，将更广泛的受众介绍给这种高潜力的分离技术。还讨论了当前提供进一步调查机会的主题。《化学和生物分子工程年度评论》第12卷的最终最终在线发布日期为2021年6月。有关修订的估算，请参见http://www.annualreviews.org/page/journal/pubdates。