In the circus, contortionists are one of the audience's favorite acts. In the laboratory, scientists may soon be able to take advantage of the contortionist abilities of fetal blood cells for non-invasive prenatal diagnostic procedures. A novel microchip has been developed that promises several advantages over existing MACS and FACS-based methods for isolating nucleated fetal red blood cells from maternal circulation.

With the growing availability of genetic markers for inherited diseases, as well as the rising average age of expecting mothers in most industrialized countries, the demand for prenatal diagnostic procedures is increasing. To date, however, most diagnostic tests are based on invasive procedures such as amniocentesis and chorionic villi sampling (CVS).

These methods are associated with a risk of spontaneous miscarriage that is unacceptable to many prospective parents, so alternatives based on the isolation of fetal cells from maternal circulation are therefore of considerable interest. The major challenge for this approach is the low frequency of fetal cells, which averages about 1 cell per 0.8 ml and therefore much lower than the occurrence of fetal cells in the amniotic fluid.

Currently available technologies for the isolation of nucleated fetal red blood cells (fNRBCs) from maternal blood center around magnetic-activated cell sorting (MACS) and fluorescence-activated cell sorting (FACS), but also include other techniques such as charge flow separation, density gradient centrifugation, immunomagnetic beads, ferrofluid suspensions, and even micromanipulation of single cells.

MACS and FACS protocols are the most advanced options for isolating fNRBCs that have been developed to date, but so far none of these various methods have yet been established in routine clinical practice. This is due, in large part, to their relatively demanding requirements in terms of time, cost, specialised equipment, and/or trained personnel. For example, the cost of most FACS machines would be a significant investment for many clinical diagnostic laboratories, and although MACS has much lower equipment costs, both procedures require hours for preparing, incubating, and manipulating samples.

A microfluidics-based method for the systematic isolation of fNRBCs from maternal blood has now been developed by researchers at the State University of New York in Albany . Led by Hisham Mohamed, of the Wadsworth Center of the New York State Department of Health, the group recently described their new biochip in an advanced online publication in the Journal of Chromatography .

Taking advantage of differences in size and deformation characteristics between fetal and maternal blood cells, the micromachined device is able to reliably purify fetal cells with no detectable maternal contamination. Although nucleated fetal red blood cells range in diameter from 9 to 12 µm, they are capable of significant deformation and can pass through channels as tiny as 2.5 by 5 µm. This stands in contrast to white blood cells, which have an only slightly larger diameter (ranging from 10 to 20 µm), yet are retained by these same channels.

The device was first tested and optimised using goose red blood cells, which are a good substitute for human fNRBCs in that both are nucleated and very similar in size. Next, human cord blood was used to successfully isolate fNRBCs for subsequent DNA analysis, which confirmed the absence of any maternal contamination. Given the economical advantages of this technique, further improvements may enable it to soon become an attractive method for routine, non-invasive prenatal diagnostics.

Article by Mohamed et al . on fetal blood cell microchip, Journal of Chromatography , June 2007 [advance online publication]

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