A high throughput genetic screening method developed by Swedish scientists could eventually lead to personalised medical treatment for genetic diseases, they claim. The method takes single cells and grows them in colonies before analysing their DNA.

Fluorescent reporters spot the difference between the DNA of two cell lines in microscale wells

The Swedish team, led by Helene Andersson-Svahn at the Royal Institute of Technology, Stockholm, combined several established technologies into an integrated system. Clones are grown in parallel from single cells held in microscale wells within a chip. The cells are then broken open to release their DNA and a polymerase chain reaction (PCR) is used to multiply the amount of DNA. This double stranded DNA is then captured onto magnetic beads and denatured to form single stranded DNA. Finally, a reporter molecule that fluoresces when it binds a particular DNA sequence is added, allowing mutations or differences between samples to be spotted. The researchers were able to use the system to distinguish cells from two human cell lines differing by one base mutation in their DNA.

The integrated system means that all the steps can be carried out on the one chip - for example, a magnetic field can be applied to keep the magnetic beads and DNA in the wells while the surrounding medium is changed. The result is the 'first study that links clonal expansion with PCR and genetic sequencing in one system,' says Andersson-Svahn. 

Ulf Landegren, an expert in molecular medicine at Uppsala University, Sweden, explains why analysing cell colonies derived from a single cell is important. 'It is becoming increasingly clear that analyses of cells in bulk may miss important factors like the division of labour among cells in a tissue and variation among cells according to state of development, cell cycle phase and influence by external factors,' he says. This is behind the 'rapidly increasing interest in single cell analyses to study the molecular properties of individual cells,' he adds. 

Andersson-Svahn says that the ultimate aim of developing the technology is to allow fast, high throughput and low cost genetic screening. Such screening would be an important step for developing personalised treatment for genetic diseases and some types of cancer, she adds.

Russell Johnson

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