Imprinted NanoVelcro Microchips for Isolation and Characterization of Circulating Fetal Trophoblasts: Toward Noninvasive Prenatal Diagnostics

被引：65

作者：

Hou, Shuang ^{[1
]}

Chen, Jie-Fu ^{[1
]}

Song, Min ^{[1
]}

Zhu, Yazhen ^{[1
,2
]}

Jan, Yu Jen ^{[1
]}

Chen, Szu Hao ^{[1
]}

Weng, Tzu-Hua ^{[1
]}

Ling, Dean-An ^{[1
]}

Chen, Shang-Fui ^{[1
]}

Ro, Tracy ^{[1
]}

Liang, An-Jou ^{[1
]}

Lee, Tom ^{[1
]}

Jin, Helen ^{[3
]}

Lo, Man ^{[3
]}

Liu, Lian ^{[3
]}

Hsiao, Yu-Sheng ^{[4
]}

Chen, Peilin ^{[4
]}

Yu, Hsiao-Hua ^{[5
]}

Tsai, Ming-Song ^{[6
]}

Pisarska, Margareta D. ^{[7
]}

Chen, Angela ^{[8
]}

Chen, Li-Ching ^{[1
,6
]}

Tseng, Hsian-Rong ^{[1
]}

机构：

[1] Univ Calif Los Angeles, Calif NanoSyst Inst, Crump Inst Mol Imaging, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

[2] Guangzhou Univ Chinese Med, Guangdong Prov Hosp TCM, Dept Pathol, Guangzhou, Guangdong, Peoples R China

[3] PacGenomics, Agoura Hills, CA 91301 USA

[4] Acad Sinica, Res Ctr Appl Sci, Taipei 115, Taiwan

[5] Acad Sinica, Inst Chem, Taipei 115, Taiwan

[6] Cathay Gen Hosp, Dept Obstet & Gynecol, Taipei 106, Taiwan

[7] Cedars Sinai Med Ctr, Dept Obstet & Gynecol, Los Angeles, CA 90048 USA

[8] Univ Calif Los Angeles, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA

来源：

ACS NANO | 2017年 / 11卷 / 08期

基金：

美国国家卫生研究院;

关键词：

noninvasive prenatal testing (NIPT); nanoVelcro assays; circulating trophoblasts; single-cell analysis; array comparative genomic hybridization (aCGH); RED-BLOOD-CELLS; TUMOR-CELLS; EMBEDDED MICROCHIPS; DNA; ENRICHMENT; ANEUPLOIDY; CAPTURE; ASSAYS; STEP; CHIP;

D O I：

10.1021/acsnano.7b03073

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Circulating fetal nucleated cells (CFNCs) in maternal blood offer an ideal source of fetal genomic DNA for noninvasive prenatal diagnostics (NIPD). We developed a class of nanoVelcro microchips to effectively enrich a subcategory of CFNCs, i.e., circulating trophoblasts (cTBs) from maternal blood, which can then be isolated with single-cell resolution by a laser capture microdissection (LCM) technique for downstream genetic testing. We first established a nanoimprinting fabrication process to prepare the LCM-compatible nanoVelcro substrates. Using an optimized cTB-capture condition and an immunocytochemistry protocol, we were able to" identify and isolate single cTBs (Hoechst+/CK7+/HLA-G+/CD45, 20 mu m > sizes > 12 mu m) on the imprinted nanoVelcro microchips. Three cTBs were polled to ensure reproducible whole genome amplification on the cTBderived DNA, "paving the way for cTB-based array comparative genomic hybridization (aCGH) and short tandem repeats analysis. Using maternal blood samples collected from expectant mothers carrying a single fetus, the cTB-derived aCGH data were able to detect fetal genders and chromosomal aberrations, which had been confirmed by standard clinical practice. Our results support the use of nanoVelcro microchips for cTB-based noninvasive prenatal genetic testing, which holds potential for further development toward future NIPD solution.

引用

页码：8167 / 8177

页数：11

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