(448f) Development of Fully Automated Microfluidic Device for High Throughput Screening of Crystallization Process

Crystallization is a key unit operation in the chemical and pharmaceutical industries for isolation, purification, and solid screening. The pharmaceutical industries rely completely on physicochemical properties to identify ideal candidate for drug manufacturing. The physicochemical properties of compounds are typically evaluated through the screening of solid forms, making drug development a time-consuming and costly process. As a result, it is imperative to optimize drug manufacturing processes and develop efficient screening technologies to reduce costs and turnaround times. The miniaturized crystallization devices, known as microfluidic crystallizers, are an emerging platform for efficient screening of crystallization process in a controlled supersaturation environment. These devices offer several advantages: (i) control over mass and heat transfer due to high surface to volume ratio, (ii) minimum solute requirement to conduct high-throughput screening, (iii) capable of detecting crystal nucleation more accurately due to miniaturized observation zone. Therefore, this work focus on developing a standalone fully-automated continuous flow microfluidic device for screening crystal polymorphs and morphology at controlled supersaturation. 3D CFD simulations are performed to optimize the design by investigating heat, mass, and momentum transfer for attaining constant temperature, supersaturation and mixing. The optimal design is fabricated using a stereolithography 3D printer and the performance of the device is evaluated by screening the polymorphs and morphology of o-aminobenzoic acid (o-ABA) crystals at different supersaturation. The experimental results reveal that continuous-flow microfluidic device is capable of resolving metastable and stable polymorphs of o-ABA. The device is then integrated with different sensors such as electrochemical sensors to measure supersaturation, Raman sensor for polymorph identification, an optical sensor for turbidity (induction time and hence nucleation rate), and growth rate measurements. The next step is to couple this device with a graphical user interface to characterize and optimize the crystallization process quickly and reliably.