Current prenatal tests for diagnosing foetal genetic abnormalities rely on invasive, “harvesting” procedures, such as amniocentesis and chorionic villus sampling. Although highly valuable, they can increase the risk of miscarriage. Whole foetal cells circulating in an expectant mother’s blood could also provide important information on foetal DNA since they contain entire genomes, but until now it has been very challenging to capture these cells because they are only present in small quantities.

The new nanoVelcro microchips developed by Hsian-Rong Tsung of the California NanoSystems Institute at the University of California at Los Angeles and colleagues can effectively enrich cTBs from blood samples. These cells can then be isolated using a technique called laser capture microdissection (LCM) for subsequent genetic testing.

The researchers (who initially developed their microchips for detecting low concentrations of tumour cells circulating in blood) made their devices by nano-imprinting them on a spin-coated PLGA substrate (see image). To enrich the cTBs, they grafted a biotinylated anti-EpCAM (which is a trophoblast surface marker) onto the imprinted nanoVelcro.

For the genetic characterization, they isolated at least three individual cTBs and pooled these together in a 0.5 mL polymerase chain reaction (PCR) tube for whole genome amplification (WGA). They then subjected the resulting amplified DNA to so-called array comparative genomic hybridization (array CGH) and short tandem repeat (STR) assays.

Results back up those obtained using conventional techniques

Tseng and colleagues tested out their technique on 5 to 10 mL blood samples taken from 15 pregnant women carrying a single foetus. They found that it was indeed able to enrich for foetal cells. What's more, the genetic testing part accurately determined the gender of the foetuses as well as certain conditions (including trisomy 21, for example) in nine of the samples. These results backed up diagnoses that had been previously performed using other routine clinical methods on these same samples.

“These pilot studies support the feasibility of conducting cTB-based non-invasive pre-natal diagnostics,” says Tseng. “We are now busy further improving the technique’s reproducibility and then heading towards a large-scale clinical trial to validate the approach,” he tells nanotechweb.org.

The nanoVelcro chip is detailed in ACS Nano.