Evidence map›Paper›PMID 31934715›Full record

ArticleLab on a chip2020

Microfluidic concentration and separation of circulating tumor cell clusters from large blood volumes.

Jon F Edd, Avanish Mishra, Taronish D Dubash, Stefan Herrera, Ridhwan Mohammad, E Kendall Williams, Xin Hong, Baris R Mutlu, John R Walsh, Fernanda Machado de Carvalho and 7 more

Open access · greenAbstract read
In one paragraph

Article in Lab on a chip, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
4.2field-weighted citation impact, top 5% of its field
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

45 citing papers in PubMed, 74 citations in OpenAlex.

  1. Review
  2. Article
  3. 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
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Label-Free Microfluidic Apheresis of Circulating Tumor Cell Clusters.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Optically Programmable Living Microrouter in Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Article
  19. Review
  20. Article
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

17 authors at 4 institutions in 2 countries.

Jon F EddBioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. mehmet_toner@hms.harvard.edu and Cancer Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.ORCID 0000-0002-2195-2938
Avanish MishraBioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. mehmet_toner@hms.harvard.edu.
Taronish D DubashCancer Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA and Harvard Medical School, Boston, MA 02115, USA.
Stefan HerreraBioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. mehmet_toner@hms.harvard.edu.ORCID 0000-0003-1436-7586
Ridhwan MohammadBioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. mehmet_toner@hms.harvard.edu.
E Kendall WilliamsBioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. mehmet_toner@hms.harvard.edu.
Xin HongCancer Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Baris R MutluBioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. mehmet_toner@hms.harvard.edu.
John R WalshBioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. mehmet_toner@hms.harvard.edu and Cancer Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Fernanda Machado de CarvalhoCancer Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Berent AldikactiBioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. mehmet_toner@hms.harvard.edu and Cancer Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.ORCID 0000-0002-8916-8007
Linda T NiemanCancer Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Shannon L StottBioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. mehmet_toner@hms.harvard.edu and Cancer Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA and Harvard Medical School, Boston, MA 02115, USA.
Ravi KapurMicroMedicine, Inc., Waltham, MA 02451, USA.
Shyamala MaheswaranCancer Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA and Harvard Medical School, Boston, MA 02115, USA.
Daniel A HaberCancer Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA and Harvard Medical School, Boston, MA 02115, USA and Howard Hughes Medical Institute, Bethesda, MD 20815, USA.
Mehmet TonerBioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. mehmet_toner@hms.harvard.edu and Shriners Hospitals for Children, Boston, Massachusetts 02114, USA.
Harvard University · USMassachusetts General Hospital · USHoward Hughes Medical Institute · USMicrosemi (Canada) · CA

Funding

Point-of care Microfluidics for Early Detection of CancerU01EB012493 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI HABER, DANIEL A., TONER, MEHMET · 2010 to 2018
$19.6M
Bio-MicroElectroMechanical Systems Resource CenterP41EB002503 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI TONER, MEHMET · 2004 to 2018
$17.4M
Modeling Metastasis and Acquired Drug Resistance Using Circulating Tumor CellsR01CA129933 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel A. Haber · 2008 to 2026
$7.5M
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
Benchmarking the Sensitivity and Specificity of the Herringbone Microfluidic Device for Rare Particle CaptureR01CA226871 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI NAHED, BRIAN VALA, STOTT, SHANNON L · 2018 to 2023
$2.3M
Howard Hughes Medical InstituteNCI NIH HHS R01 CA129933NCI NIH HHS R01 CA226871NCI NIH HHS U01 CA214297NIBIB NIH HHS P41 EB002503NIBIB NIH HHS U01 EB012493
6 · The paper itself

Abstract

Circulating tumor cells (CTCs) are extremely rare in the blood, yet they account for metastasis. Notably, it was reported that CTC clusters (CTCCs) can be 50-100 times more metastatic than single CTCs, making them particularly salient as a liquid biopsy target. Yet they can split apart and are even rarer, complicating their recovery. Isolation by filtration risks loss when clusters squeeze through filter pores over time, and release of captured clusters can be difficult. Deterministic lateral displacement is continuous but requires channels not much larger than clusters, leading to clogging. Spiral inertial focusing requires large blood dilution factors (or lysis). Here, we report a microfluidic chip that continuously isolates untouched CTC clusters from large volumes of minimally (or undiluted) whole blood. An array of 100 μm-wide channels first concentrates clusters in the blood, and then a similar array transfers them into a small volume of buffer. The microscope-slide-sized PDMS device isolates individually-spiked CTC clusters from >30 mL per hour of whole blood with 80% efficiency into enumeration (fluorescence imaging), and on-chip yield approaches 100% (high speed video). Median blood cell removal (in base-10 logs) is 4.2 for leukocytes, 5.5 for red blood cells, and 4.9 for platelets, leaving less than 0.01% of leukocytes alongside CTC clusters in the product. We also demonstrate that cluster configurations are preserved. Gentle, high throughput concentration and separation of circulating tumor cell clusters from large blood volumes will enable cluster-specific diagnostics and speed the generation of patient-specific CTC cluster lines.

Indexed as

Lab-On-A-Chip DevicesMicrofluidic Analytical TechniquesHealthy VolunteersHumansNeoplastic Cells, Circulating

Identifiers

PMID31934715
PMCPMC7469923
OpenAlexW3000588177

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.