# Non-Invasive Prenatal Diagnostics Based on Circulating Trophoblasts

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $793,038

## Abstract

PROJECT SUMMARY/ABSTRACT
The long-term goal of this revised U01 proposal is to conduct advanced development and rigorous validation of
an emerging circulating trophoblast (cTB)-based noninvasive prenatal diagnostic (NIPD) technology, capable
of i) enriching/counting cTBs from maternal blood, and ii) isolating single cTBs for genome-wide detection of
fetal genetic abnormalities during the first trimester of pregnancy. An alternative research plan is also
presented to explore the use of the same workflow for isolating and characterizing trophoblasts (TBs) in cervix
samples.
 Among potential circulating fetal nucleated cells (CFNCs) in maternal blood, cTBs are an ideal target
considering their (i) short lifespan, which excludes the presence of cTBs from prior pregnancies or
miscarriages, (ii) representation of fetal karyotype and genotype, and (iii) expression of a unique collection of
biomarkers that can be used for both enrichment and identification. However, isolating pure cTBs has been
technically challenging due to their extremely low abundance.
 Over the past decade, Dr. Tseng’s research team at UCLA has developed nanomaterial-embedded
diagnostic platforms (a.k.a., NanoVelcro Chips). To exploit the NIPD utility of NanoVelcro Chips, the team first
developed a nanoimprinting fabrication process to prepare the laser capture microdissection (LCM)-compatible
nanosubstrates in a cost-efficient and scalable manner. These chips, in conjunction with the use of capture and
immunocytochemistry (ICC) agents, exhibit superb cTB capture performance. In parallel, high-resolution
microscopy imaging and analysis software has been developed to identify and register individual cTBs on the
substrates, enabling highly accurate isolation of single cTBs by LCM. In collaboration with Dr. Pisarska, the
joint team demonstrated a workflow starting with blood processing, single cTB isolation, and DNA amplification,
all the way through whole genome profiling of cTBs by ArrayCGH and/or next generation sequencing.
 Our central hypothesis is that >10 cTBs can be harvested from 5-mL of maternal blood (>50 TBs from a
cervix sample), collected from a pregnant woman during the first trimester of pregnancy (8-12 weeks of
gestational age), and whole genome profiling of these cTBs/TBs can be used for diagnosing fetal genetic
abnormalities. Over the 5-year funding period, the proposed research will be implemented via two Specific
Aims: i) to develop, optimize and validate the proposed cTB-based NIPD technology, and ii) to conduct initial
clinical validation in pregnant women recruited from UCLA and CSMC. The joint team envisions that the
successful demonstration of the proposed cTBs-based NIPD technology will introduce a revolutionary NIPD
solution with the sensitivity and specificity of the gold standard diagnostic tests without the associated risks to
the fetus.

## Key facts

- **NIH application ID:** 10675005
- **Project number:** 5U01EB026421-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Margareta Pisarska
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $793,038
- **Award type:** 5
- **Project period:** 2019-08-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10675005

## Citation

> US National Institutes of Health, RePORTER application 10675005, Non-Invasive Prenatal Diagnostics Based on Circulating Trophoblasts (5U01EB026421-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10675005. Licensed CC0.

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