Ultrasensitive DNA Screening for Down Syndrome Offers Potential for Early Detection

MedicalResearch.com Interview with:

Zhiyong Zhang PhD Key Laboratory for the Physics and Chemistry of Nanodevices and  Department of Electronics Peking University Beijing China

Prof. Zhang

Zhiyong Zhang PhD
Key Laboratory for the Physics and Chemistry of Nanodevices
Department of Electronics
Peking University
Beijing China

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Down syndrome is caused by the presence of an extra 21st chromosome within the genome and is the most common birth defect (occurring in approximately 1 in 800 births). In the absence of a multiplexed quantitative diagnostic device, pregnant women have been examined with the ultrasound and the indirect biochemical markers (Alpha-fetoprotein, chorionic gonadotropin and free estriol) which are accompanied with a high misdiagnosis rate. And the diagnostic test (such as amniocentesis) following the wrong screening test results will bring harm to both the pregnant women and the fetuses.

Through PCR (polymerization chain reaction) amplification of the fetal DNA in the pregnant mother’s peripheral blood and fluorescence read-out, whole-genome sequencing (WGS)-based non-invasive prenatal testing (NIPT) sequences all the genomic DNA segments in parallel and quantitatively compares the percentage of different chromosomes, which increases the sensitivity for prenatal detection of Down syndrome. However, the complex instrumental setups and the resulted high processing cost present challenges for the large-scale application of WGS-based diagnosis at the point of care in the urban and rural areas of developing countries. Hence, beside the costly WGS method, there is an urgent need to develop a cost-effective NIPT biochip with simple instrumental setting, fast detection speed, high sensitivity, and programmable to multiple disease markers.

Taking advantages of we have developed a novel field effect transistor (FET) based biosensor that reveals a fast, ultra-sensitive, highly specific and cost-effective methods and someday can be used to detect fetal Down syndrome in NIPT. 

 MedicalResearch.com: What should readers take away from your report?

Response: In this work, we fabricate highly sensitive FET-based DNA biosensors in batch based on CVD-grown monolayer MoS2 film and explore their applications on non-invasive prenatal testing (NIPT) of Trisomy 21 syndrome. The biosensors are able to reliable detect target DNA fragments (chromosome 21 or 13) with a detection limit below 100 aM, a high response up to 240% and a high specificity, and are much better than all of the previously published label-free DNA biosensors. Our approach shows potential for detection of over-expression of chromosome 21 in peripheral blood of pregnant women and achieve Down’s screening.

In one word, we presented a new method for NIPT of Down syndrome which reveals several advantages and great potential. These electronic biosensors are so sensitive that traditional PCR reactions can be eliminated for low-concentration DNA detection and they support direct electrical signal read-out. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: For similar studies, researchers need to pay attention to devices uniformity and data calibration. And related blood purification and supporting data processing system has yet to be developed. For large-scale applying, it still has a long way to go.

The FET sensor can be also used as a universal sensor platform to detect most types of receptor including proteins, viruses, antibodies and nucleotides. Building a diagnostic device that could recognize multiplexed disease markers contributes to wide medical applications. Among all kinds of diagnostic devices, FET-based biosensors present advantages of label-free, low cost, high speed, small size and excellent compatibility with integrated circuits, having great potentials for label-free detections of DNA.

Citation:

Jingxia Liu, Xihua Chen, Qinqin Wang, Mengmeng Xiao, Donglai Zhong, Wei Sun, Guangyu Zhang, Zhiyong Zhang. Ultrasensitive Monolayer MoS2 Field-Effect Transistor Based DNA Sensors for Screening of Down Syndrome. Nano Letters, 2019; DOI: 10.1021/acs.nanolett.8b03818

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