Snap-on Adaptor for Microtiter Plates to Enable Continuous-Flow Microfluidic Screening and Harvesting of Crystalline Materials.

Autor:	Coliaie P; Department of Chemical Engineering, University of Illinois at Chicago, Chicago, Illinois 60607, United States., Bhawnani RR; Department of Chemical Engineering, University of Illinois at Chicago, Chicago, Illinois 60607, United States., Ali R; Department of Chemical Engineering, University of Illinois at Chicago, Chicago, Illinois 60607, United States., Kelkar MS; Center of Excellence for Isolation & Separation Technologies (CoExIST), Process R&D, AbbVie Inc., North Chicago, Illinois 60064, United States., Korde A; Center of Excellence for Isolation & Separation Technologies (CoExIST), Process R&D, AbbVie Inc., North Chicago, Illinois 60064, United States., Langston M; Pharmaceutics Research-Analytical Development, Takeda Pharmaceuticals International Co., Cambridge, Massachusetts 02139, United States., Liu C; Pharmaceutical Development, Biogen, Cambridge, Massachusetts 02142, United States., Nazemifard N; Pharmaceutics Research-Analytical Development, Takeda Pharmaceuticals International Co., Cambridge, Massachusetts 02139, United States., Patience DB; Chemical Process Development, Biogen, Cambridge, Massachusetts 02142, United States., Rosenbaum T; Bristol-Myers Squibb Co., Drug Product Science & Technology, New Brunswick, New Jersey 08901, United States., Skliar D; Bristol Myers Squibb Co., Chemical & Synthetic Development, New Brunswick, New Jersey 08901, United States., Nere NK; Department of Chemical Engineering, University of Illinois at Chicago, Chicago, Illinois 60607, United States.; Center of Excellence for Isolation & Separation Technologies (CoExIST), Process R&D, AbbVie Inc., North Chicago, Illinois 60064, United States., Singh MR; Department of Chemical Engineering, University of Illinois at Chicago, Chicago, Illinois 60607, United States.
Jazyk:	angličtina
Zdroj:	ACS omega [ACS Omega] 2023 Oct 23; Vol. 8 (44), pp. 41502-41511. Date of Electronic Publication: 2023 Oct 23 (Print Publication: 2023).
DOI:	10.1021/acsomega.3c05478
Abstrakt:	Microtiter plate assay is a conventional and standard tool for high-throughput (HT) screening that allows the synthesis, harvesting, and analysis of crystals. The microtiter plate screening assays require a small amount of solute in each experiment, which is adequate for a solid-state crystal analysis such as X-ray diffraction (XRD) or Raman spectroscopy. Despite the advantages of these high-throughput assays, their batch operational nature results in a continuous decrease in supersaturation due to crystal nucleation and growth. Continuous-flow microfluidic mixer devices have evolved as an alternate technique for efficiently screening crystals under controlled supersaturation. However, such a microfluidic device requires a minimum of two inlets per micromixer to create cyclonic flow, thereby creating physical limitations for implementing such a device for HT screening. Additionally, the monolithic design of these microfluidic devices makes it challenging to harvest crystals for post-screening analysis. Here, we develop a snap-on adapter that can be reversibly attached to a microtiter plate and convert it into a continuous-flow microfluidic mixer device. The integration of the snap-on adapter with a flow distributor and concentration gradient generator provides greater control over screening conditions while minimizing the number of independent inlets and pumps required. The three-dimensional (3D)-printed snap-on adaptor is plugged into a 24-well plate assay to demonstrate salt screening of naproxen crystals. Different naproxen salts are crystallized using four different salt formers (SFs)-sodium hydroxide, potassium hydroxide, pyridine, and arginine-and four different solvents-ethanol, methanol, isopropyl alcohol, and deionized water. The wells are further inspected under an optical microscope to identify their morphological forms and yields. The crystals are then harvested for solid-state characterization using XRD and Fourier transform infrared spectroscopy, followed by measurement of their dissolution rates. The flexibility of the snap-on adapter to fit on a wide range of microtiter plates and the ease in harvesting and analyzing crystals postscreening are two significant advantages that make this device versatile for various applications. Competing Interests: The authors declare the following competing financial interest(s): A PCT application (PCT/US20/36353) titled Continuous-Flow, Well Mixed, Microfluidic Crystallization Device for Screening Polymorphs, Morphologies and Crystallization Kinetics at Controlled Supersaturation has been filed. (© 2023 The Authors. Published by American Chemical Society.)
Databáze:	MEDLINE
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