Identification of fetal aneuploidy with dual‐probe fluorescence in situ hybridization analysis in circulating trophoblasts after enrichment using a high‐sensitivity microfluidic platform. (28th September 2021)

• Record Type: Journal Article
• Authors: Sonek, Jiri; Muller, Rolf; Muller‐Cohn, Judy; Dickerson, Janet; Garcia Lopez, Brenda; Barber‐Singh, Jennifer; Dufek, Dylan; Hiett, Adam Kinney; Buchanan, Philip
• Is Part Of: Prenatal diagnosis. Volume 41:Number 13(2021)
• Page Start: 1701
• Page End: 1708
• Publication Date: 2021-09-28
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.6046
• Languages: English
• ISSNs: 0197-3851

Abstract

Abstract: Objective: To evaluate a microfluidics‐based positive selection technology for isolating circulating trophoblasts (CTs) from peripheral blood of women whose pregnancies are affected by aneuploidy and to evaluate fetal karyotype using fluorescence in situ hybridization (FISH). Method: Ten 18‐ml samples of peripheral blood were collected consecutively from pregnant women whose fetus was affected by aneuploidy. A preservation buffer was added, and the specimens were shipped overnight to the testing laboratory at ambient temperature. The specimen was infused into the fully automated microfluidics‐based LiquidScan ® instrument without pre‐processing. This instrument contains microfluidic chips, which are coated with antibodies (anti‐huEpCAM and a proprietary antibody mixture) specific to CT surface epitopes. FISH analysis was performed on the enriched cells. Results: Fetal aneuploidy evaluated included trisomy 21 ( n = 3), trisomy 18 ( n = 1), trisomy 13 ( n = 1), monosomy X ( n = 3), and triploidy ( n = 1). CTs for analysis by FISH were identified in all samples. The average number of mononucleate cells per 1 ml of whole blood was 2.11 (range 0.38–4.63) overall and was 2.67 (range 1.13–4.63) using the proprietary combination of antibodies. FISH results were concordant with the aneuploidy based on other testing in all cases. Multinucleate cells were searched for and identified in the last seven samples (average number: 0.84/1 ml). Conclusions: Our study demonstrates that the LiquidScan ®, a high‐sensitivity microfluidic platform, can enrich circulating trophoblasts (mononucleate and multinucleate). FISH can then be used to detect fetal aneuploidy. Key points: What is already known about this topic? Fetal trophoblasts are found in maternal circulation during pregnancy Existing methods used to enrich circulating trophoblasts are time‐intensive and expensive What does this study add? We introduce an automated and inexpensive microfluidic platform to enrich circulating trophoblasts (mononucleate and multinucleate) A larger number of fetal cells was captured than reported in previous publications We identified fetal aneuploidy (trisomies 21, 18, and 13, monosomy X, triploidy) in captured cells using fluorescence in situ hybridization