Separation of biomacromolecules for medical diagnostics, pharmaceutical applications, and bioprocess is a multi-million dollar effort where even the minutest increase in the separation efficiency has a very healthy impact on the process or application. Antibiotics, proteins, and DNA are some key examples of biomolecules where new techniques and approaches for separation are required and needed.

In addition to improved capillary electrophoresis, modified structured gels, smaller scales (micro- and nano-fluidics) appear to be promising choices for improving separation efficiency in micro-separation of bio-macromolecules; within this framework, researchers have focused the efforts on few main aspects: Since electrokinetic-based approaches dominate the way that micro and nano-fluidics work, in addition to the “media”, electrical fields are key to perform the separation. Reports in the literature focus on the “external operating variables”, i.e. magnitude, directions and time-nature of the electrical field and on the “internal variables” of the material or media, i.e. the architecture or morphology of the material used as a media for separation. A third case is the addition of attachments to the biomolecule to modify its electrophoretic mobility in solution and a fourth approach, although not frequently used, is the combination of the efforts just described.

In this presentation, the authors will summarize recent work on models based on fundamental principles that allow for a systematic understanding of the role of orthogonal fields and how they can be used to effectively improve separation. A scaling-based argument, rooted on area-averaging approaches, and within convective-diffusive transport will be used to compute optimal separation times. We will illustrate the approach for idealized geometries of capillary channels and for Couette-based regimes. Future efforts for possible further research will be also outlined.