Cargando…
A Pilot Proof-Of-Principle Analysis Demonstrating Dielectrophoresis (DEP) as a Glioblastoma Biomarker Platform
Extracellular vesicles (EVs) are small, membrane-bound particles released by all cells that have emerged as an attractive biomarker platform. We study the utility of a dielectrophoretic (DEP) micro-chip device for isolation and characterization of EVs derived from plasma specimens from patients with...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635369/ https://www.ncbi.nlm.nih.gov/pubmed/31311947 http://dx.doi.org/10.1038/s41598-019-46311-8 |
_version_ | 1783435870032887808 |
---|---|
author | Lewis, Jean Alattar, Ali A. Akers, Johnny Carter, Bob S. Heller, Michael Chen, Clark C. |
author_facet | Lewis, Jean Alattar, Ali A. Akers, Johnny Carter, Bob S. Heller, Michael Chen, Clark C. |
author_sort | Lewis, Jean |
collection | PubMed |
description | Extracellular vesicles (EVs) are small, membrane-bound particles released by all cells that have emerged as an attractive biomarker platform. We study the utility of a dielectrophoretic (DEP) micro-chip device for isolation and characterization of EVs derived from plasma specimens from patients with brain tumors. EVs were isolated by DEP chip and subjected to on-chip immunofluorescence (IF) staining to determine the concentration of glial fibrillary acidic protein (GFAP) and Tau. EVs were analyzed from the plasma samples isolated from independent patient cohorts. Glioblastoma cell lines secrete EVs enriched for GFAP and Tau. These EVs can be efficiently isolated using the DEP platform. Application of DEP to clinical plasma samples afforded discrimination of plasma derived from brain tumor patients relative to those derived from patients without history of brain cancer. Sixty-five percent (11/17) of brain tumor patients showed higher EV-GFAP than the maximum observed in controls. Ninety-four percent (16/17) of tumor patients showed higher EV-Tau than the maximum observed in controls. These discrimination thresholds were applied to plasma isolated from a second, independent cohort of 15 glioblastoma patients and 8 controls. For EV-GFAP, we observed 93% sensitivity, 38% specificity, 74% PPV, 75% NPV, and AUC of 0.65; for EV-Tau, we found 67% sensitivity, 75% specificity 83% PPV, 55% NPV, and AUC of 0.71 for glioblastoma diagnosis. This proof-of-principle study provides support for DEP-IF of plasma EVs for diagnosis of glioblastoma. |
format | Online Article Text |
id | pubmed-6635369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-66353692019-07-24 A Pilot Proof-Of-Principle Analysis Demonstrating Dielectrophoresis (DEP) as a Glioblastoma Biomarker Platform Lewis, Jean Alattar, Ali A. Akers, Johnny Carter, Bob S. Heller, Michael Chen, Clark C. Sci Rep Article Extracellular vesicles (EVs) are small, membrane-bound particles released by all cells that have emerged as an attractive biomarker platform. We study the utility of a dielectrophoretic (DEP) micro-chip device for isolation and characterization of EVs derived from plasma specimens from patients with brain tumors. EVs were isolated by DEP chip and subjected to on-chip immunofluorescence (IF) staining to determine the concentration of glial fibrillary acidic protein (GFAP) and Tau. EVs were analyzed from the plasma samples isolated from independent patient cohorts. Glioblastoma cell lines secrete EVs enriched for GFAP and Tau. These EVs can be efficiently isolated using the DEP platform. Application of DEP to clinical plasma samples afforded discrimination of plasma derived from brain tumor patients relative to those derived from patients without history of brain cancer. Sixty-five percent (11/17) of brain tumor patients showed higher EV-GFAP than the maximum observed in controls. Ninety-four percent (16/17) of tumor patients showed higher EV-Tau than the maximum observed in controls. These discrimination thresholds were applied to plasma isolated from a second, independent cohort of 15 glioblastoma patients and 8 controls. For EV-GFAP, we observed 93% sensitivity, 38% specificity, 74% PPV, 75% NPV, and AUC of 0.65; for EV-Tau, we found 67% sensitivity, 75% specificity 83% PPV, 55% NPV, and AUC of 0.71 for glioblastoma diagnosis. This proof-of-principle study provides support for DEP-IF of plasma EVs for diagnosis of glioblastoma. Nature Publishing Group UK 2019-07-16 /pmc/articles/PMC6635369/ /pubmed/31311947 http://dx.doi.org/10.1038/s41598-019-46311-8 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Lewis, Jean Alattar, Ali A. Akers, Johnny Carter, Bob S. Heller, Michael Chen, Clark C. A Pilot Proof-Of-Principle Analysis Demonstrating Dielectrophoresis (DEP) as a Glioblastoma Biomarker Platform |
title | A Pilot Proof-Of-Principle Analysis Demonstrating Dielectrophoresis (DEP) as a Glioblastoma Biomarker Platform |
title_full | A Pilot Proof-Of-Principle Analysis Demonstrating Dielectrophoresis (DEP) as a Glioblastoma Biomarker Platform |
title_fullStr | A Pilot Proof-Of-Principle Analysis Demonstrating Dielectrophoresis (DEP) as a Glioblastoma Biomarker Platform |
title_full_unstemmed | A Pilot Proof-Of-Principle Analysis Demonstrating Dielectrophoresis (DEP) as a Glioblastoma Biomarker Platform |
title_short | A Pilot Proof-Of-Principle Analysis Demonstrating Dielectrophoresis (DEP) as a Glioblastoma Biomarker Platform |
title_sort | pilot proof-of-principle analysis demonstrating dielectrophoresis (dep) as a glioblastoma biomarker platform |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635369/ https://www.ncbi.nlm.nih.gov/pubmed/31311947 http://dx.doi.org/10.1038/s41598-019-46311-8 |
work_keys_str_mv | AT lewisjean apilotproofofprincipleanalysisdemonstratingdielectrophoresisdepasaglioblastomabiomarkerplatform AT alattaralia apilotproofofprincipleanalysisdemonstratingdielectrophoresisdepasaglioblastomabiomarkerplatform AT akersjohnny apilotproofofprincipleanalysisdemonstratingdielectrophoresisdepasaglioblastomabiomarkerplatform AT carterbobs apilotproofofprincipleanalysisdemonstratingdielectrophoresisdepasaglioblastomabiomarkerplatform AT hellermichael apilotproofofprincipleanalysisdemonstratingdielectrophoresisdepasaglioblastomabiomarkerplatform AT chenclarkc apilotproofofprincipleanalysisdemonstratingdielectrophoresisdepasaglioblastomabiomarkerplatform AT lewisjean pilotproofofprincipleanalysisdemonstratingdielectrophoresisdepasaglioblastomabiomarkerplatform AT alattaralia pilotproofofprincipleanalysisdemonstratingdielectrophoresisdepasaglioblastomabiomarkerplatform AT akersjohnny pilotproofofprincipleanalysisdemonstratingdielectrophoresisdepasaglioblastomabiomarkerplatform AT carterbobs pilotproofofprincipleanalysisdemonstratingdielectrophoresisdepasaglioblastomabiomarkerplatform AT hellermichael pilotproofofprincipleanalysisdemonstratingdielectrophoresisdepasaglioblastomabiomarkerplatform AT chenclarkc pilotproofofprincipleanalysisdemonstratingdielectrophoresisdepasaglioblastomabiomarkerplatform |