On-Chip Protein Separation and Enrichment

Proteins are central to biological research, diagnostics and the development of new therapeutics. Yet their analysis often depends on workflows in which separation, concentration and detection are performed using different instruments. These workflows can be slow, require substantial sample volumes and result in the loss of low-abundance proteins. Miniaturising the individual steps is not sufficient. The fundamental challenge is to control the transport of diverse proteins within a single microfluidic environment and to deliver selected fractions at concentrations suitable for subsequent analysis.

This PhD will develop new principles for the integrated extraction and enrichment of proteins on-chip. The research will investigate how electrical forces, fluid transport and surface interactions can be jointly controlled to manipulate proteins according to differences in their physicochemical properties. Particular attention will be given to dynamic and recirculating separation strategies that allow proteins to experience a controllable separation field repeatedly. Such approaches could extend the effective separation path without requiring a proportionally larger device and could create new opportunities to progressively enrich selected protein fractions.

The project will combine micro- and nanofluidic device engineering, electrokinetics, surface chemistry, transport modelling and experimental protein analysis. It will examine how device geometry, operating conditions and protein-surface interactions determine separation resolution, recovery and concentration gain. Strategies to suppress sample loss and undesired adsorption will be studied together with methods for collecting, retaining or further processing the separated fractions. The research will progress from well-defined protein mixtures towards more heterogeneous samples relevant to protein characterization and analytical workflows.

The central scientific question is how a compact fluidic system can distinguish, concentrate and route proteins while preserving their structural and functional properties to connect directly with downstream analytical methods and support faster protein characterization, biomarker analysis and iterative protein-engineering workflows using substantially smaller sample volumes.

The work will depart from one of the strategies investigated previously within our group, specifically the use of field-gradient, depletion zones and ion-selective membranes, coupled to online or downstream separation, to achieve the following objectives:

1. Upconcentration of protein of interest to surpass the limit-of-detection of golden-standard methods in drug discovery (e.g. MS, affinity measurement).
2. Promote the selective extraction of proteins of interest downstream from synthetic operations.

Identify methods of promoting programmable extraction of different proteins using the same device and to create staged separation for increased purity.