Optimization of designs for spatial multi-dimensional separations

The aim of the thesis is to investigate the potential of multi-dimensional liquid chromatography (LC) and to formulate guidelines for the optimal design of spatial separation devices. Chapter 1 provides an introduction to multi-dimensional LC.
In Chapter 2 a Pareto-optimization approach is applied to various types of three-dimensional systems. The efficiency is evaluated in terms of achieving the maximum peak capacity in the minimum analysis time. A peak capacity of several hundreds of thousands of peaks may be achievable within a few hours using an xLC×xLC×tLC system.
In Chapter 3 microfluidic chips are considered that feature one first-dimension (1D) separation channel, 16 second-dimension (2D) channels, and 256 or 1024 third-dimension (3D) channels with specified lengths. The performance of column-based tLC×tLC systems for the separation of proteins is expected to be considerably exceeded.
In Chapter 4 design aspects of two main types of flow distributors - radially interconnected (RI) and bifurcating (BF) - are discussed based on computational fluid dynamics (CFD). Guidelines are formulated for designing flow distributors and the effects of imperfections or blockages are studied.
In Chapter 5 the theoretical approach described in Chapter 4 is validated in practice, using chips fabricated by micromilling. CFD simulations of the distribution of analytes in two-dimensional systems are presented. Flow confinement within the 1D channel by applying flow resistance or implementing constrictions in the segments near the outlets of the flow distributor is demonstrated by CFD and confirmed experimentally. Chapter 6 contains some reflections on the development of microfluidic devices for multi-dimensional separations.