Biosensors: Morpholino Offers You More

Molecular biologists and geneticists often use DNA microarrays to detect DNA, measure gene expression levels and detect the single-nucleotide polymorphisms that are responsible for various genetic diseases. A DNA microarray has tens of thousands of biosensors on its surface; each biosensor contains a short DNA fragment, known as a probe, for recognizing DNA targets. Ideally, the DNA biosensor should have high sensitivity (the ability to detect very low concentrations of targets), high specificity (the ability to distinguish the difference between similar targets) and high stability (the ability to withstand wear and tear over many cycles).

In recent years, scientists have taken an interest in silicon nanowire (SiNW) biosensors as an option to improve microarray performance. SiNW biosensors are more sensitive than conventional biosensors because probes are functionalized onto the silicon surface, which has a large surface-to-volume ratio. However, SiNW biosensors rely on an electric field for DNA detection, so using negatively charged DNA fragments as probes may interfere with measurement.

Guo Jun Zhang and co-workers at the A*STAR Institute of Microelectronics1 have now overcome this problem by using ‘Morpholinos’ as probes. Morpholinos, first discovered in 1985, are synthetic molecules that structurally resemble naturally occurring DNA molecules. Each Morpholino molecule comprises a nucleic acid base, a morpholine ring and a non-ionic phosphorodiamidate linkage. More importantly, Morpholinos have many properties that are superior to DNA, including higher stability and higher specificity.

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