On chip separation: large molecules pass the speed camera first

What molecule or particle passes the finishline first? A good way to split a fluid sample into its separate parts is: organize a contest in a micro-channel. The largest parts will pass the optical detector first, the smaller ones follow at short distance. This principle of ‘hydrodynamic chromatography’ is now also possible on a chip. ‘On-chip’ separation is faster, needs tiny samples and uses minimum of harmful solvents. Marko Blom developed this separation chip within the MESA+ research institute of the University of Twente. He presents his PhD-work on December 13, 2002.

The separation channel Blom has developed is not deeper than one micron, it is one millimeter in width and some six to eight centimeters long. It has been fabricated in silicon or silicate glass. Thanks to this compact geometry, the separation is fast: bigger molecules move faster, smaller ones follow. A light-sensitive cell detects the fastest ones first. Colour characteristics provide additional information about the particle or molecule: therefore at the start of the ‘race’, fluorescent markers can be added to the fluid, for example.

Hydrodynamic chromatography (HDC) is a well-known separation technique for particles and large molecules, but the resolution of current methods is far from optimal. HDC is usually applied in a fluid column, filled with non-porous particles that create, with the tiny spaces inbetween, the same effect as a narrow channel. On-chip separation results in a better resolution because the geometry is better defined than the pores between the particles in a conventional column, that are divided in a rather arbitrary way. Within just a few minutes Blom can, for example, fully separate little polystyrene balls. The new chip is particularly interesting for analysis of large molecules like polymers. For biomolecules, it works as well: for example analysis of DNA-components.

Lab-on-chip
A microsystem like this new separation chip has more advantages than the ones mentioned above: it is possible to add all kinds of functionality. It is not just the separation itself that takes place on-chip, but also detection and fluid preparation can be done. Blom has built a with a viscosity sensor: a small bridge over the channel slightly disturbs the fluid. The difference in pressure can be detected optically. The system is a new lab-on-chip, systems that are for large amounts of analyses at the same time.

Blom’s research is part of the research orientation MicroChemical Systems, within the MESA+ research institute of the University of Twente in The Netherlands (www.mesaplus.utwente.nl). It has been financially supported by the Dutch Technology Foundation STW (www.stw.nl). Blom has done his research in close cooperation with the Polymer Analysis group of the University of Amsterdam.