(394m) Solvent Compatible Polymer Based Microfluidics for Applications in Pharmaceutical Industry

Poly(dimethylsiloxane) or PDMS has been the prime material of choice in microfluidics mainly because PDMS enables  simple, inexpensive fabrication using soft-lithographic technique, which facilitates rapid prototyping of devices.  Other advantages, such as biocompatibility, optical transparency, low young’s modulus, have led to the use of PDMS-based microfluidics for several applications in chemistry and biology.  However, PDMS suffers from several limitations, including poor solvent compatibility, small molecules absorption, and limited compatibility with analytical techniques, low mechanical rigidity, and issues with large-scale fabrication.  Traditionally, silicon and glass have addressed some of PDMS’ deficiencies, but the complex and expensive fabrication procedures, material fragility, and incompatibility with a wide range of analytical techniques have limited their applications.

Polymeric materials that enable simple, inexpensive fabrication while addressing PDMS limitations are emerging as attractive candidates for developing microfluidic devices.  Since no single polymer will satisfy all the requirements of the end application, we have developed hybrid devices comprising multiple layers of different polymers to overcome the deficiencies resulting from using single polymers.  Our hybrid-microfluidic platforms, ranging from simple single channel devices to complex multilayer devices, comprise thin layers of different polymers, viz. cyclic olefin copolymer (COC), Teflon FEP, perfluoropolyether (SIFEL), thiolene, and PDMS. 

Here, we demonstrate the application of these devices in the pharmaceutical industry for two specific examples.  In the first example, we developed microfluidic platforms for screening solid forms (salt, cocrystal and polymorph) of pharmaceutical compounds with different additives (e.g., salt or cocrystal formers) employing several modes of crystallization. These platforms allow for solid form screening much early in the drug development cycle when only small quantities of drug (~10 mg) are available thereby aiding in expediting the drug development process.  The platforms consist of multiple layers of COC-PDMS-PDMS-COC-PDMS-thiolene and COC-PDMS-SIFEL-SIFEL-Teflon-SIFEL-thiolene.  In the second example, we have developed devices for liquid-liquid extraction, where (a) thiolene-glass devices were used to evaluate distribution coefficient of drugs in octanol-water mixture for in-vitro drug uptake studies and (b) COC-SIFEL-SIFEL-glass devices were used to purify radioisotopes with applications in synthesis of cancer imaging agents.  The material choice was guided by several considerations, including compatibility with solvents (e.g., alcohols, toluene, DMSO, chloroform) and analytical techniques (X-ray, Raman), the strength of bond between heterogeneous polymers bonded via surface activation by plasma or chemical treatment, amenability for high-resolution fabrication, and mechanical robustness as well as reliability of the assembly for long-term experiments.