Evidence map›Paper›PMID 29568081›Full record

ArticleScientific reports2018

An integrated flow cytometry-based platform for isolation and molecular characterization of circulating tumor single cells and clusters.

Neha Bhagwat, Keely Dulmage, Charles H Pletcher, Ling Wang, William DeMuth, Moen Sen, David Balli, Stephanie S Yee, Silin Sa, Frances Tong and 5 more

Abstract readValidation Study
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed.

  1. Article
  2. Extracellular vesicles isolation: a focus on magnetic beads-assisted platforms.Frontiers in bioengineering and biotechnology · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Neha BhagwatDivision of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Keely DulmageBD Technologies and Innovation, Research Triangle Park, NC, USA.
Charles H PletcherDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ling WangBD Technologies and Innovation, Research Triangle Park, NC, USA.
William DeMuthDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Moen SenDivision of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
David BalliDivision of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Stephanie S YeeDivision of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-3469-9775
Silin SaBD Biosciences, San Jose, CA, USA.
Frances TongBD Technologies and Innovation, Research Triangle Park, NC, USA.
Liping YuBD Biosciences, San Jose, CA, USA.
Jonni S MooreDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ben Z StangerDivision of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Eric P DixonBD Technologies and Innovation, Research Triangle Park, NC, USA.
Erica L CarpenterDivision of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. erical@upenn.edu.

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Robert H. Vonderheide · 1985 to 2026
$222.3M
Real-time monitoring of circulating pancreatic tumor cells and clustersR01CA207643 · NCI · UNIVERSITY OF PENNSYLVANIA · PI CARPENTER, ERICA · 2016 to 2021
$2.3M
NCI NIH HHS P30 CA016520NCI NIH HHS R01 CA207643
6 · The paper itself

Abstract

Comprehensive molecular analysis of rare circulating tumor cells (CTCs) and cell clusters is often hampered by low throughput and purity, as well as cell loss. To address this, we developed a fully integrated platform for flow cytometry-based isolation of CTCs and clusters from blood that can be combined with whole transcriptome analysis or targeted RNA transcript quantification. Downstream molecular signature can be linked to cell phenotype through index sorting. This newly developed platform utilizes in-line magnetic particle-based leukocyte depletion, and acoustic cell focusing and washing to achieve >98% reduction of blood cells and non-cellular debris, along with >1.5 log-fold enrichment of spiked tumor cells. We could also detect 1 spiked-in tumor cell in 1 million WBCs in 4/7 replicates. Importantly, the use of a large 200μm nozzle and low sheath pressure (3.5 psi) minimized shear forces, thereby maintaining cell viability and integrity while allowing for simultaneous recovery of single cells and clusters from blood. As proof of principle, we isolated and transcriptionally characterized 63 single CTCs from a genetically engineered pancreatic cancer mouse model (n = 12 mice) and, using index sorting, were able to identify distinct epithelial and mesenchymal sub-populations based on linked single cell protein and gene expression.

Indexed as

AnimalsCell Line, TumorCell SeparationDisease Models, AnimalFlow CytometryGene Expression ProfilingHumansLeukocyte Reduction ProceduresLiquid BiopsyMagnetsMiceNeoplastic Cells, CirculatingPancreatic NeoplasmsSingle-Cell Analysis

Identifiers

PMID29568081
PMCPMC5864750

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.