A new, sensitive field-effect transistor-based biosensor made from 2D molybdenum disulphide could be used in non-invasive prenatal testing for Down syndrome. The device, which is functionalized with gold nanoparticles containing DNA probes that specifically target DNA fragments of chromosome 21, is sensitive to this DNA at concentrations as low as 0.1 femtomoles/litre.
Down, or trisomy 21, syndrome is caused by the presence of an extra copy of chromosome 21 within the genome and is the most common birth defect, occurring in roughly one in 800 births. Current screening techniques include ultrasound scans or indirect biomarkers tests – for example, testing for α-fetoprotein, chorionic gonadotropin and free estriol. However, these have limited accuracy and high misdiagnosis rates. Amniocentesis, which does provide a definitive diagnosis, is not without risk to both the future mother and foetus, and whole-genome sequencing – a highly accurate technique – is slow and expensive because it needs to amplify all genomic segments and sequences owing to the extremely low, sub-femtomole, concentrations of foetal DNA.
FET-based DNA biosensor chip
A team led by Zhiyong Zhang of the Key Laboratory for the Physics and Chemistry of Nanodevices and Department of Electronics at Peking University, has now put forward a fast, simple, sensitive and cost-effective FET-based DNA biosensor chip made from monolayer MoS2 (grown by chemical vapour deposition).
The researchers functionalized the MoS2 with gold nanoparticles and then topped these with probe DNA sequences. These DNAs specifically capture target DNA fragments of chromosome 21 in maternal blood samples. When bound to the probes, these fragments cause the electric current measured across the FET sensor to drop.
The researchers believe that the main mechanism behind this drop is the p-doping of the MoS2 channel by the probe DNA or target DNA, which should lead to a decrease in the number of electrons within local regions of the MoS2 channel.
Ultrahigh detection limit
Compared with previously reported MoS2 FET biosensors, the new sensor has an ultrahigh detection limit of 100 attomoles/litre, a high response of 240% and excellent selectivity. A real-time test also showed that the biosensor responds to the target DNA at concentrations as low as 1 fM/L. All these properties satisfy the essential requirement for Down syndrome screening, says the team.
According to Zhang and colleagues, the high sensitivity and large response of the FET biosensor come mainly thanks to two factors. The first is the high-quality and uniform monolayer MoS2 used as the channel in the FET that is extremely sensitive to surface dopants. Second, the gold nanoparticles employed, which are of the right size and right density, functionalized on the MoS2 channel serve as excellent linkers for the probe DNA.
And that is not all: as well as detecting chromosome 21 for Down syndrome, the sensor might also be used as a universal platform to detect receptors like proteins, viruses, antibodies, and nucleotides simply by replacing the probe molecules, say the researchers.
Full details of the research are reported in Nano Letters 10.1021/acs.nanolett.8b03818.
