Evidence map›Paper›PMID 30474100›Full record

ArticleLab on a chip2018

Ultrasensitive quantification of tumor mRNAs in extracellular vesicles with an integrated microfluidic digital analysis chip.

Peng Zhang, Jennifer Crow, Divya Lella, Xin Zhou, Glenson Samuel, Andrew K Godwin, Yong Zeng

Abstract read
In one paragraph

Article in Lab on a chip, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 10% 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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Ultrafast Detection of Exosomal RNAsACS applied nano materials · 2021
    Article
  17. Article
  18. Article
  19. Review
  20. Latest advances in extracellular vesicles: from bench to bedside.Science and technology of advanced materials · 2019
    Review
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

7 authors at 3 institutions in 1 country.

Peng ZhangDepartment of Chemistry, University of Kansas, Lawrence, KS, USA. yongz@ku.edu.
Jennifer Crow
Divya Lella
Xin Zhou
Glenson Samuel
Andrew K Godwin
Yong Zeng
University of Kansas · USKansas City Kansas Community College · USNational Marrow Donor Program · US

Funding

Understanding the mechanobiology of stem cells in a microengineered 3D cardiac tissue environment with cardiomyopathyP20GM103638 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI HOLMSTROM, ERIK D · 2012 to 2021
$22.1M
Integrated exosomes profiling for minimally invasive diagnosis and monitoring of cancerR33CA214333 · NCI · UNIVERSITY OF KANSAS LAWRENCE · PI GODWIN, ANDREW K., SAMUEL, GLENSON · 2017 to 2019
$1.2M
Integrated Microfluidic Exosome Profiling for Early Detection of CancerR21CA186846 · NCI · UNIVERSITY OF KANSAS LAWRENCE · PI ZENG, YONG · 2014 to 2016
$645k
Integrated Digital Microfluidic Platforms for Next-Generation GlycomicsR21CA207816 · NCI · UNIVERSITY OF KANSAS LAWRENCE · PI ZENG, YONG · 2016 to 2017
$585k
Microfluidic Integrative Circulating miRNA Profiling for Cancer DiagnosisR21EB024101 · NIBIB · UNIVERSITY OF KANSAS LAWRENCE · PI DOYLE, PATRICK S, ZENG, YONG · 2017 to 2018
$411k
NCI NIH HHS R21 CA186846NCI NIH HHS R21 CA207816NCI NIH HHS R33 CA214333NIBIB NIH HHS R21 EB024101NIGMS NIH HHS P20 GM103638
6 · The paper itself

Abstract

Extracellular vesicles (EVs) present a promising liquid biopsy for cancer diagnosis. However, it remains a daunting challenge to quantitatively measure molecular contents of EVs including tumor-associated mRNAs. Herein, we report a configurable microwell-patterned microfluidic digital analysis platform combined with a dual-probe hybridization assay for PCR-free, single-molecule detection of specific mRNAs in EVs. The microwell array in our device is configurable between the flow-through assay mode for enhanced hybridization capture and tagging of mRNAs and the digital detection mode based on femtoliter-scale enzymatic signal amplification for single-molecule counting of surface-bound targets. Furthermore, a dual-probe hybridization assay has been developed to enhance the sensitivity of the digital single-molecule detection of EV mRNAs. Combining the merits of the chip design and the dual-probe digital mRNA hybridization assay, the integrated microfluidic system has been demonstrated to afford quantitative detection of synthetic GAPDH mRNA with a LOD as low as 20 aM. Using this technology, we quantified the level of GAPDH and EWS-FLI1 mRNAs in EVs derived from two cell lines of peripheral primitive neuroectodermal tumor (PNET), CHLA-9 and CHLA-258. Our measurements detected 64.6 and 43.5 copies of GAPDH mRNA and 6.5 and 0.277 copies of EWS-FLI1 fusion transcripts per 105 EVs derived from CHLA-9 and CHLA-258 cells, respectively. To our knowledge, this is the first demonstration of quantitative measurement of EWS-FLI1 mRNA copy numbers in Ewing Sarcoma (EWS)-derived EVs. These results highlight the ultralow frequency of tumor-specific mRNA markers in EVs and the necessity of developing highly sensitive methods for analysis of EV mRNAs. The microfluidic digital mRNA analysis platform presented here would provide a useful tool to facilitate quantitative analysis of tumor-associated EV mRNAs for liquid biopsy-based cancer diagnosis and monitoring.

Indexed as

Microfluidic Analytical TechniquesBiomarkers, TumorCell Line, TumorEquipment DesignExtracellular VesiclesHumansLimit of DetectionNucleic Acid HybridizationRNA, MessengerBiomarkers, TumorRNA, Messenger

Identifiers

PMID30474100
PMCPMC6310142
OpenAlexW2901523872

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.