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DNA sequencing on a chip


10 February 2010

Scientists in the US have developed a cheap and easy to use DNA sequencing method to help with medical diagnosis. 

Genome sequencing is a costly but important tool in biomedical research used for the study of genetic disease and cancer. Common sequencing methods only sequence one or two DNA bases at a time in several cycles, which makes them costly to run in terms of time and reagents required. Now Xiaohua Huang and colleagues at the University of California, San Diego have come up with a sequencing technique called sequencing by denaturation (SBD), which can be performed on a chip with a single integrated microfluidic device. 

In Huang's method, fluorescently labelled nucleotides are randomly incorporated into the DNA during replication. This results in fragments of different lengths, each labelled with a fluorescent molecule corresponding to its ending base type. Next these fragments are heated and, because shorter fragments have a lower melting temperature, sequentially denatured from the shortest fragment to the longest. By monitoring the decrease in fluorescence during this process, the signal can be analyzed to determine the base sequence of the target DNA template. 

Integrated microfluidic devic

An integrated microfluidic device can sequence DNA by denaturation

The major advantages of SBD include the short sequencing run, low cost reagents and its ease of use, says Huang. 'This device has the capability for performing high-speed fluorescence imaging while biomedical reactions with precisely controlled temperature profiles take place,' he adds. 'Although the read length is quite limited, due to its simplicity, SBD has the potential to bring down the cost of large-scale sequencing drastically.' 

Jeremy Edwards, an expert in functional genomics tool development at the University of New Mexico, Alberquerque, US says this is an extremely interesting and novel sequencing approach which has the tremendous advantage of simplicity and cost. 'I would think that this approach would be very useful for genotyping in the future where full sequencing is not necessary,' he adds. 

However, additional work is needed to advance the technique further and ultimately enable rapid and real time readout from single DNA molecules with up to 10,000 bases, concludes Huang. 

Philippa Ross 

 

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Link to journal article

DNA sequencing by denaturation: experimental proof of concept with an integrated fluidic device
Ying-Ja Chen, Eric E. Roller and Xiaohua Huang, Lab Chip, 2010, 10, 1153
DOI: 10.1039/b921417h

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