Solvent compatible microfluidic platforms for pharmaceutical solid form screening

Sachit Goyal, Aristotle E. Economou, Theodore Papadopoulos, Elizabeth M. Horstman, Geoff G.Z. Zhang, Yuchuan Gong, Paul J.A. Kenis

Research output: Contribution to journalArticlepeer-review


We describe a microfluidic platform with enhanced solvent compatibility to screen solid forms of pharmaceutical parent compounds including salts, cocrystals, and their crystal forms via controlled solvent evaporation and antisolvent addition techniques. The platform enables on-chip combinatorial mixing of parent compound, auxiliary materials, or non-solvents in a 24- to 72-well array (∼100-200 nL per well). This approach enables screening with very small quantities of material per condition compared to traditional screening approaches that require larger volumes, ∼100 μL per well. Compatibility with (i) polar as well as non-polar organic solvents commonly employed in crystallization of pharmaceuticals, such as ethanol, methanol, tetrahydrofuran, acetonitrile, chloroform, hexane, and toluene, (ii) Raman spectroscopy used for on-line identification of the resulting solids was achieved by using a perfluoropolyether-based microfluidic platform. Integration of a hybrid thin layer assembly of elastomeric PDMS-SIFEL-SIFEL ensures that pneumatic valving capabilities are retained. This assembly was sandwiched between layers of cyclic-olefin copolymer (COC) at the top and Teflon FEP or COC (depending on the solvent) at the bottom to yield a physically rigid, Raman compatible crystallization chip. In addition, a solvent-impermeable thiolene layer patterned with evaporation channels was employed to permit control over the rate of solvent evaporation for solvent evaporation experiments. The resulting hybrid microfluidic platforms enabled enhanced compatibility with a variety of polar and non-polar organic solvents such as methanol, ethanol, isopropyl alcohol, acetonitrile, tetrahydrofuran, hexane, heptane, and toluene, which is especially critical for antisolvent crystallization experiments. In solvent evaporation experiments with these platforms the rate of solvent evaporation can be controlled consistently (5-20 nL h-1), thereby facilitating nucleation and crystal growth. Model compounds, theophylline and carbamazepine, were used to validate the platform's ability to screen for cocrystals via solvent evaporation and for polymorphs via antisolvent addition. On-chip Raman analysis was used to identify different cocrystals and polymorphs.

Original languageEnglish (US)
Pages (from-to)13286-13296
Number of pages11
JournalRSC Advances
Issue number16
StatePublished - 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)


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