Microchip System Incorporates Tiny Sieve That Sorts Biomarkers

A new microchip system promises to speed up the separation and sorting of biomolecules such as proteins. The work is important because it could help scientists better detect certain molecules associated with diseases, potentially leading to earlier diagnoses or treatments.

The microchip system has an extremely tiny sieve structure built into it that can sort through continuous streams of biologic fluids and separate proteins accurately by size. Conventional separation methods employ gels, which are slower and more labor-intensive to process. The new microchip system could sort proteins in minutes, as compared to the hours necessary for gel-based systems.

The system was developed by a Massachusetts Institute of technology (MIT; Cambridge, MA, USA) team headed by Professor Jongyoon Han and was described in the February 5, 2006, issue of Nature Nanotechnology.

The new technology is an advance from a one-dimensional sieve structure reported by the same MIT group last year. The key to this new advance, called an anisotropic nanofluidic sieving structure, is that the scientists have designed the anisotropic sieve in two orthogonal dimensions (at a right angle), which enables rapid continuous-flow separation of the biologic sample. This allows continuous isolation and harvesting of subsets of biomolecules that scientists want to study. And that increases the probability of detecting even the smallest number of molecules in the sample.

With this technology we can isolate interesting proteins faster and more efficiently. And because it can process such small biologically relevant entities, it has the potential to be used as a generic molecular sieving structure for a more complex, integrated biomolecule preparation and analysis system, said Professor Han.

Professor Han and Jianping Fu therefore devised the anisotropic sieve that is embedded into a silicon chip. A biologic sample containing different proteins is placed in a sample reservoir above the chip. The sample is then run through the sieve of the chip continuously. The chip is designed with a network of microfluidic channels surrounding the sieve, and the anisotropy (directional property) in the sieve causes proteins of different sizes to follow distinct migration trajectories, leading to efficient continuous-flow separation. The current sieve has an array of nanofluidic filters of about 55 nm, or billionths of a meter, wide.

The proteins to be sorted are forced to take two orthogonal paths. Each path is engineered with different sieving characters. When proteins of different sizes are injected into the sieve under applied electric fields, they will separate into different streams based on size, Professor Han explained. At the bottom of the chip the separated proteins are collected in individual chambers. Scientists then can test the proteins.

An advantage of the microchip is that it can have so many different pore sizes, and unlike gels, it is possible to design an exact pore size to increase the separation accuracy. That in turn can help scientists look for so-called biomarkers, or proteins that can reveal that disease is present, and thus help researchers develop diagnostics and treatments for the disease.




Related Links:
MIT