利用微孔膜高精度协同控制的溶析结晶传质过程研究

Antisolvent crystallization is a kind of crystal preparation technology which is widely used in the biology, medicine, military industry, etc. The key problems of the control of antisolvent crystallization process are the high precision addition and the high efficiency of micro mixing of the antisolvent with the solution, and then the controlling stable nucleation and growth of the crystal after the addition of the antisolvent..In this project, we introduce the microporous membrane to control the mass transfer of antisolvent crystallization, the antisolvent transfer the membrane channel under the pressure or temperature gradient and then mix with the solution at the membrane intreface directely. The nucleation and crystal growth occurr and are controlled simultaneously at the high supersaturated region. Due to the micrometer scale porous channel of the membrane, the micro mixing can be significantly improved and the mass tranfer control accuracy can be increased by 1 or 2 order of magnitudes compared to the existing droplet method with the millimeter scale mixing; At the same time, microporous membranes are controllable and uniformly distributed in a microporous membrane separator that provides the stable environment for the nucleation and crystal growth. The existing local, random in crystallizer transfer to the uniform and stable nucleation in microporous membrane separator, leaching agent is added and the crystallization process in membrane separator is collaborative controlled. With the research of this project, we will develop a new type of high precision mass transfer control mechanism for the high precision addition and the high efficiency of micro mixing of the antisolvent, and enrich and develop the mass transfer control theory of antisolvent crystallization, realize the manufacture of the crystals with desire particle properties.

溶析结晶是一种广泛应用于生物、医药、军工等领域的晶体制备技术。溶析结晶传质过程的两个关键问题是（1）溶析剂与溶液的高效微观混合；（2）溶析剂加入后的晶体可控成核与生长。本项目提出在溶析结晶中引入微孔膜，协同控制传质过程：溶析剂在膜两侧化学势差的推动下透过膜孔道，在微孔膜界面与溶液直接混合，形成高浓度过饱和区，进而实现晶体成核和生长的协同控制。相比于现有毫米尺度的滴加方法，采用微孔膜的亚微米尺度孔道控制加入溶析剂，混合尺度大大缩小，可将传质速率控制精度提高1~2个数量级；同时，由于微孔膜可控、均匀地分布于膜分离器中，将结晶器内局部、随机成核，转变为微孔膜界面均匀、稳定成核，实现溶析剂加入和结晶过程在膜分离器中的协同连续控制。本项目的研究将建立一种溶析剂定量加入、高效微观混合的新型传质机制，丰富和发展溶析结晶的高精度传质控制理论，实现具有优良颗粒特性晶体产品的连续化制备。

溶析结晶是一种广泛应用于生物、医药、军工等领域的晶体制备技术。溶析结晶传质过程的两个关键问题是（1）溶析剂与溶液的高效微观混合；（2）溶析剂加入后的晶体可控成核与生长。.本项目提出在溶析结晶中引入微孔膜，协同控制传质过程：相比于现有毫米尺度的滴加方法，采用微孔膜的亚微米尺度孔道控制加入溶析剂，混合尺度大大缩小，传质速率控制精度提高了1~2个数量级；同时，由于微孔膜可控、均匀地分布于膜分离器中，将结晶器内局部、随机成核转变为微孔膜界面均匀稳定成核，实现溶析剂加入和结晶过程在膜分离器中的协同连续控制。.本项目围绕膜材料制备理论、膜溶析结晶的液膜构建机制、调控理论、多级过程优化理论和应用基础取得了系统性的创新成果，ACS Nano, AIChE J, Cryst Growth Des, Chem Eng Sci, ACS Appl Mater Inter, J Membr Sci, Engineering, Lab Chip, 化工学报等发表论文51篇，项目成果被基金委网站报道；受邀撰写《分离过程耦合强化》、《膜技术手册》等专著专章。授权中国发明专利11项，授权美国、日本专利各1项。.项目组成员作为核心骨干，荣获基金委创新研究群体1个，科技部创新团队1个，中国石化联合会创新团队1个。项目研究团队快速成长：2人荣获青年长江，引进1人获国家青年千人，4人晋升为教授/副教授，培养博士/硕士4/21人。累计荣获国家科技进步二等奖等国家级、省部级科技和人才奖励10余项，日内瓦国际发明展特别金奖1项。.同时，积极开展学术交流，2017年以来一直在国际顶级化工会议AIChE年会、中国化工学会年会上组织专题分会，累计举办和参加国际/国内重要学术会议18次；担任国内外学术主席7人次，大会报告、邀请报告12次。.该项目研发的膜法溶析结晶调控技术，已经建立了系统的基于膜溶析结晶的高效分离和晶体产品制备的新理论和新应用技术，应用于高盐废水脱盐、车用尿素、赤藓糖醇等领域，促进我国化工、医药及相关产业发展。同时，还为反应结晶中的多相体系混合和调控提供新思路，有望成为非常有潜力的理论基础和技术储备。