Evidence map›Paper›PMID 39746954›Full record

ArticleNature communications2025

Tumor cell-based liquid biopsy using high-throughput microfluidic enrichment of entire leukapheresis product.

Avanish Mishra, Shih-Bo Huang, Taronish Dubash, Risa Burr, Jon F Edd, Ben S Wittner, Quinn E Cunneely, Victor R Putaturo, Akansha Deshpande, Ezgi Antmen and 23 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing 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

28 citing papers in PubMed.

  1. Review
  2. Towards liquid biopsy-based analysis of antitumour immunity.Nature reviews. Clinical oncology · 2026
    Review
  3. Review
  4. Review
  5. Article
  6. Dynamic monitoring of antibody drug conjugates targeting TROP2 or HER2 in breast cancer using circulating tumor cells.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  9. Article
  10. Review
  11. Review
  12. Article
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  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors.

Avanish Mishra *Center for Engineering in Medicine and Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Shih-Bo Huang *Krantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA, 02129, USA.ORCID 0000-0002-1048-2344
Taronish DubashKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA, 02129, USA.
Risa BurrKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA, 02129, USA.
Jon F EddCenter for Engineering in Medicine and Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Ben S WittnerKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA, 02129, USA.ORCID 0000-0001-5657-9849
Quinn E CunneelyCenter for Engineering in Medicine and Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Victor R PutaturoCenter for Engineering in Medicine and Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Akansha DeshpandeCenter for Engineering in Medicine and Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Ezgi AntmenCenter for Engineering in Medicine and Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Kaustav A GopinathanCenter for Engineering in Medicine and Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.ORCID 0000-0002-4082-1052
Keisuke OtaniKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA, 02129, USA.ORCID 0000-0002-8275-0651
Yoshiyuki MiyazawaKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA, 02129, USA.ORCID 0000-0002-8416-2394
Ji Eun KwakKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA, 02129, USA.
Sara Y GuayKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA, 02129, USA.
Justin KellyKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA, 02129, USA.
John WalshCenter for Engineering in Medicine and Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Linda T NiemanKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA, 02129, USA.
Isabella GallerDivision of Hematology Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, 02114, USA.
PuiYee ChanDivision of Hematology Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, 02114, USA.
Michael S LawrenceKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA, 02129, USA.ORCID 0000-0002-1307-459X
Ryan J SullivanDivision of Hematology Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, 02114, USA.ORCID 0000-0001-5344-6645
Aditya BardiaDivision of Hematology Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, 02114, USA.
Douglas S MicalizziKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA, 02129, USA.
Lecia V SequistDivision of Hematology Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, 02114, USA.
Richard J LeeDivision of Hematology Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, 02114, USA.
Joseph W FransesDivision of Hematology Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, 02114, USA.
David T TingKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA, 02129, USA.ORCID 0000-0002-3261-2322
Patricia A R BrunkerDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Shyamala MaheswaranKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA, 02129, USA.
David T MiyamotoKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA, 02129, USA. dmiyamoto@mgh.harvard.edu.ORCID 0000-0003-3692-8823
Daniel A HaberKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA, 02129, USA. DHABER@mgh.harvard.edu.ORCID 0000-0003-1378-6551
Mehmet TonerCenter for Engineering in Medicine and Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA. mehmet_toner@hms.harvard.edu.ORCID 0000-0002-3647-3665

Funding

Bio-MicroElectroMechanical Systems Resource CenterP41EB002503 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI TONER, MEHMET · 2004 to 2018
$17.4M
Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7M
High-flow microfluidics of leukapheresis blood products for functional analysis of breast circulating tumor cellsR01CA255602 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI HABER, DANIEL A., MAHESWARAN, SHYAMALA · 2021 to 2025
$3.2M
Microfluidic isolation and molecular analysis of circulating tumor cells for the study of neuroendocrine transdifferentiation in prostate cancerU01CA268933 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Melissa Abel, Mehmet Toner · 2022 to 2026
$3.0M
Metastasis and biophysics of clusters of circulating tumor cells in the microcirculationU01CA214297 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI HABER, DANIEL A., MAHESWARAN, SHYAMALA · 2018 to 2022
$2.9M
Microfluidic sorting of lung cancer cells from leukapheresis product as an alternative to metastatic tumor biopsyR01CA260304 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI HABER, DANIEL A., MAHESWARAN, SHYAMALA · 2021 to 2025
$2.2M
Precision Apheresis: stem cell isolation from patients with sickle cell disease for gene therapy using high-throughput microfluidicsK25HL169816 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Avanish Mishra · 2023 to 2026
$550k
Microfluidic Apheresis to Isolate Circulating Tumor ClustersR21CA260989 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI TONER, MEHMET · 2022 to 2023
$428k
NCI NIH HHS R01 CA255602NCI NIH HHS R01 CA260304NCI NIH HHS R21 CA260989NCI NIH HHS U01 CA214297NCI NIH HHS U01 CA268933NHLBI NIH HHS K25 HL169816NIBIB NIH HHS P41 EB002503NIGMS NIH HHS T32 GM144273U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA255602U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R21CA260989U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U01CA214297U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) K25HL169816U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB) P41EB002503
6 · The paper itself

Abstract

Circulating Tumor Cells (CTCs) in blood encompass DNA, RNA, and protein biomarkers, but clinical utility is limited by their rarity. To enable tumor epitope-agnostic interrogation of large blood volumes, we developed a high-throughput microfluidic device, depleting hematopoietic cells through high-flow channels and force-amplifying magnetic lenses. Here, we apply this technology to analyze patient-derived leukapheresis products, interrogating a mean blood volume of 5.83 liters from seven patients with metastatic cancer. High CTC yields (mean 10,057 CTCs per patient; range 100 to 58,125) reveal considerable intra-patient heterogeneity. CTC size varies within patients, with 67% overlapping in diameter with WBCs. Paired single-cell DNA and RNA sequencing identifies subclonal patterns of aneuploidy and distinct signaling pathways within CTCs. In prostate cancers, a subpopulation of small aneuploid cells lacking epithelial markers is enriched for neuroendocrine signatures. Pooling of CNV-confirmed CTCs enables whole exome sequencing with high mutant allele fractions. High-throughput CTC enrichment thus enables cell-based liquid biopsy for comprehensive monitoring of cancer.

Indexed as

LeukapheresisNeoplastic Cells, CirculatingAneuploidyBiomarkers, TumorExome SequencingFemaleHigh-Throughput Nucleotide SequencingHumansLiquid BiopsyMaleMicrofluidic Analytical TechniquesMicrofluidicsNeoplasmsProstatic NeoplasmsSingle-Cell AnalysisBiomarkers, Tumor

Identifiers

PMID39746954
PMCPMC11696112

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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.