| Crystallization is a separation and purification technique,and it plays an important role in pharmaceutical manufacturing industry.In recent years,emulsion-based platforms have been development and widely applied for generating highly products.However,the traditional on-chip approaches suffer from the limitations including unstable crystallization environment,mixed crystal forms,and broad size distribution.Microfluidic chip has a lot of characteristics,such as stable environment,short experimental time,etc.Therefore,this project researches crystallization on a microfluidic chip.In this thesis,a flow-free droplet-based microfluidic chip,which not only provides a small and stable mini crystallization environment,but also solves the problems of mixed crystals and broad size distribution.In the proposed method,a solution is trapped in an array of microwells that are degassed due to the feature of the material of the chip-PDMS,and then the silicone oil was covered to prevent rapid evaporation.The droplets were formed isolated in each microwell driven by surface tension,and the crystals were formed as array in the chip.The droplet-based microfluidic chip in this study is divided into two kinds:(1)The chip for crystallization,which is used for yielding high throughput and independent droplets in microwell array to generate separate and consistent highly crystals.Glycine and insulin crystallization was researched with the chip,it laid the groundwork for the analysis of amino acid and protein crystallization.(2)The chip for concentration gradient,which is a new chip extended from the foregoing one and the new chip was used for achieving a concentration gradient profile.A test by means of the so-called color gradient proved the feasibility of the new chip,and further the glycine and sodium chloride crystal gradients demonstrated the usefulness of this chip in the crystallization.The following conclusions can be got from this thesis study:(1)Spiral-striated glycine structure of periodical crystalline agglomerates(PAs),asymmetric crystallization of droplet,crystalline shift,and shock wave expansion of crystallization energy releasing phenomenon can be formed,which has not been reported by anybody in literature.Further,the glycine crystal with new shape,PAs along with its dynamic crystallization progress was captured by the image with the microscope,and its components and crystal form were identified as a form by X-ray diffraction analysis.Finally,independent bovine insulin crystals with the same shape were obtained first in this thesis study.Therefore,the chip for crystallization can produce crystals with coincident form,shape and size reliably,narrowing particle size distribution,improving the ratio of single crystal and laying solid foundation for drug manufacturing.(2)Color gradients and crystal gradients were generated in the chip,which simplified the exploration of concentration effects on crystallization.The results showed that the simple and efficient microfluidic chip can also form a temperature or pH gradients,and such a chip has some potential application. |
