'Microsieve' sorts biomarkers faster
biomolecules, such as proteins, in search of the tell-tale signs of
disease.
The US research team from the Massachusetts Institute of Technology (MIT) have created a microchip with a tiny sieve structure built into it that can sort through continuous streams of biological fluids and separate proteins accurately by size, according to a report in the latest issue of Nature Nanotechnology.
The new technology promises to sort through large molecules faster than existing techniques and could help scientists detect biomarkers - proteins associated with diseases - better, potentially leading to earlier diagnoses or treatments.
Conventional separation methods employ gels, which are slower and more labour-intensive to process. The new microchip system could sort proteins in minutes, as compared to the hours necessary for gel-based systems.
The new technology is an advance from a one-dimensional sieve structure reported by the same group last year. The team have since designed a so-called anisotropic sieve, made in two dimensions at a right angle to each other. This enables scientists to continuously isolate and harvest the biomolecules they are interested in studying and, in turn, increases the chances of detecting molecules only found in tiny amounts.
"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 Jongyoon Han, who is head of the MIT team.
Han noted that until the late 1990s, most advances in biological laboratory equipment were aimed at the Human Genome Project and discoveries related to DNA. However, because of the vital role proteins play in almost all biological processes, researchers began to focus their attention on proteins.
One obstacle has been the lack of good laboratory tools with which to prepare biological samples to analyze proteins, said Han.
"I shifted my attention from DNA into the area of protein separation around 2002," Han said. "But the field was using decades-old gel electrophoresis technology. There is a big gap in the need for technology in this area."
The team therefore devised a sieve that is embedded into a silicon chip. A biological sample containing different proteins is placed in a sample reservoir above the chip. The sample is then continuously run through the sieve of the chip.
The chip is designed with a network of tiny fluid channels surrounding the sieve.
"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," Han explained.
At the bottom of the chip the separated proteins are collected in individual chambers. Scientists then can test the proteins.. While other scientists have used similar continuous flow techniques to separate large molecules like long DNA, the MIT team succeeded with the tinier proteins.
"This is the first time physiologically relevant molecules like proteins have been separated in such a manner," said Han. "We can separate the molecules in about a minute with the current device versus hours for gels."
Another 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 researchers look for biomarkers, that can reveal when a disease is present, and thus develop diagnostics and treatments for the disease.
"Sample preparation is critical in detecting more biomarker signals," said Han.
