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A high-throughput multi-microfluidic crystal generator (MMicroCryGen) platform for facile screening of polymorphism and crystal morphology for pharmaceutical compounds

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journal contribution
posted on 20.11.2018, 10:55 by Elena Simone, J. McVeigh, Nuno M. Reis, Zoltan Nagy
In this work, a novel multi-microfluidic crystallization platform called MMicroCryGen is presented, offering a facile methodology for generating individual crystals for fast and easy screening of the polymorphism and crystal habit of solid compounds. The MMicroCryGen device is capable of performing 8 × 10 cooling crystallization experiments in parallel using 8 disposable microcapillary film strips, each requiring less than 25 μL of solution. Compared to traditional microfluidic systems, the MMicroCryGen platform does not require complex fluid handling; it can be directly integrated with a 96-well microplate and it can also work in a “dipstick” mode. The produced crystals can be safely and directly observed inside the capillaries by optical and spectroscopic techniques. The platform was validated by performing a number of independent experimental runs for: (1) polymorph and hydrate screening of ortho-aminobenzoic acid, succinic acid and piroxicam; (2) co-crystal form screening of the p-toluenesulfonamide/triphenylphosphine oxide system; (3) studying the effect of o-toluic acid on ortho-aminobenzoic cooling crystallization (effect of structurally related additives). In all three cases, all known solid forms were identified with a single experiment using ∼200 μL of solvent and just a few micrograms of the solid material. The MMicroCryGen is simple to use, inexpensive and it provides increased flexibility compared to traditional crystallization techniques, being an effective new microfluidic solution for solid form screening in pharmaceutical, fine chemicals, food and agrochemical industries.

Funding

This work has been funded through the European Research Council grant no. [280106-CrySys].

History

School

  • Aeronautical, Automotive, Chemical and Materials Engineering

Department

  • Chemical Engineering

Published in

Lab on a Chip

Citation

SIMONE, E. ... et al, 2018. A high-throughput multi-microfluidic crystal generator (MMicroCryGen) platform for facile screening of polymorphism and crystal morphology for pharmaceutical compounds. Lab on a Chip, 18 (15), pp.2235-2245.

Publisher

© The Royal Society of Chemistry

Version

AM (Accepted Manuscript)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/

Acceptance date

01/09/2017

Publication date

2018

Notes

This paper was accepted for publication in the journal Lab on a Chip and the definitive published version is available at https://doi.org/10.1039/C8LC00301G

ISSN

1473-0197

eISSN

1473-0189

Language

en

Exports