Jump to main content
Jump to site search

Issue 22, 2011
Previous Article Next Article

A microfluidic platform for pharmaceutical salt screening

Author affiliations

Abstract

We describe a microfluidic platform comprised of 48 wells to screen for pharmaceutical salts. Solutions of pharmaceutical parent compounds (PCs) and salt formers (SFs) are mixed on-chip in a combinatorial fashion in arrays of 87.5-nanolitre wells, which constitutes a drastic reduction of the volume of PC solution needed per condition screened compared to typical high throughput pharmaceutical screening approaches. Nucleation and growth of salt crystals is induced by diffusive and/or convective mixing of solutions containing, respectively, PCs and SFs in a variety of solvents. To enable long term experiments, solvent loss was minimized by reducing the thickness of the absorptive polymeric material, polydimethylsiloxane (PDMS), and by using solvent impermeable top and bottom layers. Additionally, well isolation was enhanced via the incorporation of pneumatic valves that are closed at rest. Brightfield and polarized light microscopy and Raman spectroscopy were used for on-chip analysis and crystal identification. Using a gold-coated glass substrate and minimizing the thickness of the PDMS control layer drastically improved the signal-to-noise ratio for Raman spectra. Two drugs, naproxen (acid) and ephedrine (base), were used for validation of the platform's ability to screen for salts. Each PC was mixed combinatorially with potential SFs in a variety of solvents. Crystals were visualized using brightfield polarized light microscopy. Subsequent on-chip analyses of the crystals with Raman spectroscopy identified four different naproxen salts and five different ephedrine salts.

Graphical abstract: A microfluidic platform for pharmaceutical salt screening

Back to tab navigation

Publication details

The article was received on 16 Jul 2011, accepted on 15 Sep 2011 and first published on 28 Sep 2011


Article type: Paper
DOI: 10.1039/C1LC20645A
Lab Chip, 2011,11, 3829-3837

  •   Request permissions

    A microfluidic platform for pharmaceutical salt screening

    M. R. Thorson, S. Goyal, B. R. Schudel, C. F. Zukoski, G. G. Z. Zhang, Y. Gong and P. J. A. Kenis, Lab Chip, 2011, 11, 3829
    DOI: 10.1039/C1LC20645A

Search articles by author

Spotlight

Advertisements