The Gentle Fetal Genome
Can lab-on-a-chip technology enable extensive – yet noninvasive – prenatal screening?
William Aryitey |
Invasive testing on a fetus is never desirable but can be unavoidable, which is why so many researchers are working on new and improved noninvasive prenatal tests (NIPT). One such research team is using inertial microfluidics within a lab-on-a-chip device to collect circulating fetal trophoblasts in maternal peripheral blood (1). Here, we speak with Marnie Winter, first author and research associate at the University of South Australia, to find out how the method differs from existing NIPT.
What is the origin of your work?
We have been working in the field of rare cell isolation for a number of years, with a particular interest in the isolation of circulating tumor cells, which poses a similar technical challenge to the isolation of circulating fetal cells from pregnant women’s blood. Recently, the field of prenatal screening has been revolutionized by the introduction of NIPT based on circulating cell-free fetal DNA. The technique has now gained broad clinical acceptance for the detection of a number of common genetic disorders; however, the technology is limited. By relying on fragments of DNA in the maternal blood stream, such tests are unable to provide information on the full range of potential genetic abnormalities.
Our experience in rare cell isolation and the great diagnostic potential of circulating fetal cells, which provide a whole intact genome, prompted us to refocus our efforts towards the isolation of those cells. From our perspective, that is a more elusive goal – but one that could have a huge impact on prenatal screening.
How far are you from having such an impact?
Our work thus far demonstrates the potential for inertial microfluidics to enrich circulating fetal cells. The isolation of these cells from blood has been attempted many times in the past, but is extremely challenging, so the field has stagnated. However, modern technologies (ours included) give us hope that we can reliably isolate these cells from all pregnancies. By combining our cell isolation (and the whole fetal genome contained within) with cutting-edge genomic technology, we can offer much more comprehensive prenatal screening. We believe that cell-based NIPT will form a part of the prenatal screening landscape in the near future.
How do you see your lab-on-a-chip technology fitting into the pathologist’s workflow?
In general, lab-on-a-chip concepts enable the manipulation of clinical specimens with very high accuracy and efficiency – and can often be completely automated. As a result, these technologies have a high potential to simplify and facilitate a pathologist’s workflow. In our specific case, inertial microfluidics is an extremely gentle, rapid, and cost-effective way to enrich rare cells. None of the standard enrichment approaches have been clinically useful in circulating fetal cells because to their extreme rarity and stringent sample requirements.
For the test to be clinically viable, we need fully integrated technology that requires minimal user input. We are currently working on creating technology to address this. At the same time, we are working with industry partners and geneticists to develop genetic analysis techniques specifically for low-number or single circulating fetal cells.
Our research is supported by the Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, and also by the National Health and Medical Research Council (Australia). There are a number of key collaborators for this project, including Majid Warkiani from the University of Technology Sydney, Tristan Hardy from SA Pathology, and Dierdre Zander-Fox from Monash IVF group.
- M Winter at al., “Isolation of circulating fetal trophoblasts using inertial microfluidics for noninvasive prenatal testing”, Adv Mater Technol, 3 (2018).