High-throughput isolation of fetal nucleated red blood cells by multifunctional microsphere-assisted inertial microfluidics

Wang, Zixiang; Cheng, Lin; Wei, Xiaoyun; Cai, Bo; Sun, Yue; Zhang, Yuanzhen; Liao, Lei; Zhao, Xingzhong

doi:10.1007/s10544-020-00531-2

Cited by 17 publications

(17 citation statements)

References 41 publications

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“…Microfluidics, also called lab-on-a-chip, has recently been used extensively in the biomedical field. The chips can concentrate cell separation, biochemical reactions, and assay analysis in micro-/nanoscale pores, which facilitates cell separation as well as downstream analysis [ 14 , 64 – 77 ]. According to the research needs, the internal structure of chips can be designed to achieve precise control of the fluid [ 65 , 78 , 79 ].…”

Section: Separation Methods Based On Micro/nanotechnologiesmentioning

confidence: 99%

“…Current fetal genetic biomarkers in NIPD are mainly derived from cell-free fetal DNA (cffDNA) and fNRBCs in the peripheral blood of pregnant women [ 10 – 13 ]. Since the discovery of cffDNA in the pregnancy peripheral blood in 1997, numerous studies have illustrated the great contribution of cffDNA in fetal aneuploidy screening [ 14 – 17 ]. However, cffDNA is not only minimal in the first trimester but also could contain a mixture of fetal DNA with a large amount of maternal DNA in the placental mosaic.…”

Section: Introductionmentioning

confidence: 99%

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Noninvasive prenatal diagnosis targeting fetal nucleated red blood cells

Chen

Sutlive

et al. 2022

J Nanobiotechnol

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Noninvasive prenatal diagnosis (NIPD) aims to detect fetal-related genetic disorders before birth by detecting markers in the peripheral blood of pregnant women, holding the potential in reducing the risk of fetal birth defects. Fetal-nucleated red blood cells (fNRBCs) can be used as biomarkers for NIPD, given their remarkable nature of carrying the entire genetic information of the fetus. Here, we review recent advances in NIPD technologies based on the isolation and analysis of fNRBCs. Conventional cell separation methods rely primarily on physical properties and surface antigens of fNRBCs, such as density gradient centrifugation, fluorescence-activated cell sorting, and magnetic-activated cell sorting. Due to the limitations of sensitivity and purity in Conventional methods, separation techniques based on micro-/nanomaterials have been developed as novel methods for isolating and enriching fNRBCs. We also discuss emerging methods based on microfluidic chips and nanostructured substrates for static and dynamic isolation of fNRBCs. Additionally, we introduce the identification techniques of fNRBCs and address the potential clinical diagnostic values of fNRBCs. Finally, we highlight the challenges and the future directions of fNRBCs as treatment guidelines in NIPD. Graphical Abstract

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Section: Separation Methods Based On Micro/nanotechnologiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Noninvasive prenatal diagnosis targeting fetal nucleated red blood cells

Chen

Sutlive

et al. 2022

J Nanobiotechnol

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Section: Microfluidic Technologies For Fnrbc Isolationmentioning

confidence: 99%

“…However, circulating NRBCs captured onto the chip were irreversible and could not be recovered, thus limiting their application for downstream analysis. Lately, our group presented a microsphere-assisted inertial microfluidic chip that achieved high-throughput fNRBC capture and release (Figure d) . In this work, gelatin-coated silicon microspheres were first utilized to bond fNRBCs, thus enlarging the size of fNRBCs, followed by purification through the spiral chip, and finally, captured fNRBCs were released by enzyme degradation of the gelatin nanofilm.…”

Section: Microfluidic Technologies For Fnrbc Isolationmentioning

confidence: 99%

Emerging Microfluidic Technologies for the Detection of Circulating Tumor Cells and Fetal Nucleated Red Blood Cells

Wei

Chen

Guo

et al. 2021

ACS Appl. Bio Mater.

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Blood tests have been a powerful tool for the clinical analysis of many diseases. With the advances in microfluidic technology, two more specific indicators from the circulation system, namely, emerging "liquid biopsy" of circulating tumor cells (CTCs) and fetal nucleated red blood cells (fNRBCs), can be screened and analyzed as a simple blood test for the noninvasive diagnosis of cancers as well as fetal disorders. The unique feature of precisely manipulating a trace of fluid endows microfluidic devices with the ability to isolate CTCs or fNRBCs from numerous blood cells with high performance, which undoubtedly facilitates biomedical applications of these two kinds of rare cells. In this review, advanced developments in microfluidic technologies focusing on the detection and sorting of rare CTCs and fNRBCs from peripheral blood are summarized. The development of microfluidic devices incorporated with various multifunctional microstructures and nanomaterials for enhancing the sensitivity, purity, and viability of CTC or fNRBC detection enables CTC molecular analysis and fNRBC-based noninvasive prenatal diagnosis (NIPD). These microfluidics-based approaches provide great potential opportunities in noninvasive cancer diagnosis or NIPD applications.

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“…The release of fetal cells from the microspheres is achieved by enzymatic treatment. A fetal cell capture efficiency of approximately 81%, a purity of 83%, and a viability of cell release >80% were calculated using spiked samples [ 78 ]. The technology is very suggestive, and robust evidence is needed about its practical application when tested on a large series of patients.…”

Section: New Approachesmentioning

confidence: 99%

Isolation and Enrichment of Circulating Fetal Cells for NIPD: An Overview

et al. 2021

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Prenatal diagnosis plays a crucial role in clinical genetics. Non-invasive prenatal diagnosis using fetal cells circulating in maternal peripheral blood has become the goal of prenatal diagnosis, to obtain complete fetal genetic information and avoid risks to mother and fetus. The development of high-efficiency separation technologies is necessary to obtain the scarce fetal cells from the maternal circulation. Over the years, multiple approaches have been applied, including choice of the ideal cell targets, different cell recovering technologies, and refined cell isolation yield procedures. In order to provide a useful tool and to give insights about limitations and advantages of the technologies available today, we review the genetic research on the creation and validation of non-invasive prenatal diagnostic testing protocols based on the rare and labile circulating fetal cells during pregnancy.

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High-throughput isolation of fetal nucleated red blood cells by multifunctional microsphere-assisted inertial microfluidics

Cited by 17 publications

References 41 publications

Noninvasive prenatal diagnosis targeting fetal nucleated red blood cells

Noninvasive prenatal diagnosis targeting fetal nucleated red blood cells

Emerging Microfluidic Technologies for the Detection of Circulating Tumor Cells and Fetal Nucleated Red Blood Cells

Isolation and Enrichment of Circulating Fetal Cells for NIPD: An Overview

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