Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Acoustic Enrichment of Heterogeneous Circulating Tumor Cells and Clusters from Metastatic Prostate Cancer Patients

Magnusson, Cecilia LU ; Augustsson, Per LU ; Undvall Anand, Eva LU ; Lenshof, Andreas LU orcid ; Josefsson, Andreas ; Welén, Karin ; Bjartell, Anders LU ; Ceder, Yvonne LU orcid ; Lilja, Hans LU orcid and Laurell, Thomas LU (2024) In Analytical Chemistry 96(18). p.6914-6921
Abstract

BACKGROUND: There are important unmet clinical needs to develop cell enrichment technologies to enable unbiased label-free isolation of both single cell and clusters of circulating tumor cells (CTCs) manifesting heterogeneous lineage specificity. Here, we report a pilot study based on the microfluidic acoustophoresis enrichment of CTCs using the CellSearch CTC assay as a reference modality.

METHODS: Acoustophoresis uses an ultrasonic standing wave field to separate cells based on biomechanical properties (size, density, and compressibility), resulting in inherently label-free and epitope-independent cell enrichment. Following red blood cell lysis and paraformaldehyde fixation, 6 mL of whole blood from 12 patients with metastatic... (More)

BACKGROUND: There are important unmet clinical needs to develop cell enrichment technologies to enable unbiased label-free isolation of both single cell and clusters of circulating tumor cells (CTCs) manifesting heterogeneous lineage specificity. Here, we report a pilot study based on the microfluidic acoustophoresis enrichment of CTCs using the CellSearch CTC assay as a reference modality.

METHODS: Acoustophoresis uses an ultrasonic standing wave field to separate cells based on biomechanical properties (size, density, and compressibility), resulting in inherently label-free and epitope-independent cell enrichment. Following red blood cell lysis and paraformaldehyde fixation, 6 mL of whole blood from 12 patients with metastatic prostate cancer and 20 healthy controls were processed with acoustophoresis and subsequent image cytometry.

RESULTS: Acoustophoresis enabled enrichment and characterization of phenotypic CTCs (EpCAM
+, Cytokeratin
+, DAPI
+, CD45
-/CD66b
-) in all patients with metastatic prostate cancer and detected CTC-clusters composed of only CTCs or heterogeneous aggregates of CTCs clustered with various types of white blood cells in 9 out of 12 patients. By contrast, CellSearch did not detect any CTC clusters, but detected comparable numbers of phenotypic CTCs as acoustophoresis, with trends of finding a higher number of CTCs using acoustophoresis.

CONCLUSION: Our preliminary data indicate that acoustophoresis provides excellent possibilities to detect and characterize CTC clusters as a putative marker of metastatic disease and outcomes. Moreover, acoustophoresis enables the sensitive label-free enrichment of cells with epithelial phenotypes in blood and offers opportunities to detect and characterize CTCs undergoing epithelial-to-mesenchymal transitioning and lineage plasticity.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Analytical Chemistry
volume
96
issue
18
pages
6914 - 6921
publisher
The American Chemical Society (ACS)
external identifiers
  • pmid:38655666
  • scopus:85191839641
ISSN
1520-6882
DOI
10.1021/acs.analchem.3c05371
project
High Throughput Microfluidic Cell Nanoparticle Handling by Molecular and Thermal Gradient Acoustic Focusing
Akustisk flödescytometri för cancerdiagnostik
Akustisk gradientfokusering för separation av biopartiklar
language
English
LU publication?
yes
id
205b4eed-2e7f-45bc-9d40-7315e7d8fb55
date added to LUP
2024-04-28 11:14:19
date last changed
2025-11-12 09:51:27
@article{205b4eed-2e7f-45bc-9d40-7315e7d8fb55,
  abstract     = {{<p>BACKGROUND: There are important unmet clinical needs to develop cell enrichment technologies to enable unbiased label-free isolation of both single cell and clusters of circulating tumor cells (CTCs) manifesting heterogeneous lineage specificity. Here, we report a pilot study based on the microfluidic acoustophoresis enrichment of CTCs using the CellSearch CTC assay as a reference modality.</p><p>METHODS: Acoustophoresis uses an ultrasonic standing wave field to separate cells based on biomechanical properties (size, density, and compressibility), resulting in inherently label-free and epitope-independent cell enrichment. Following red blood cell lysis and paraformaldehyde fixation, 6 mL of whole blood from 12 patients with metastatic prostate cancer and 20 healthy controls were processed with acoustophoresis and subsequent image cytometry.</p><p>RESULTS: Acoustophoresis enabled enrichment and characterization of phenotypic CTCs (EpCAM<br>
 +, Cytokeratin<br>
 +, DAPI<br>
 +, CD45<br>
 -/CD66b<br>
 -) in all patients with metastatic prostate cancer and detected CTC-clusters composed of only CTCs or heterogeneous aggregates of CTCs clustered with various types of white blood cells in 9 out of 12 patients. By contrast, CellSearch did not detect any CTC clusters, but detected comparable numbers of phenotypic CTCs as acoustophoresis, with trends of finding a higher number of CTCs using acoustophoresis.<br>
 </p><p>CONCLUSION: Our preliminary data indicate that acoustophoresis provides excellent possibilities to detect and characterize CTC clusters as a putative marker of metastatic disease and outcomes. Moreover, acoustophoresis enables the sensitive label-free enrichment of cells with epithelial phenotypes in blood and offers opportunities to detect and characterize CTCs undergoing epithelial-to-mesenchymal transitioning and lineage plasticity.</p>}},
  author       = {{Magnusson, Cecilia and Augustsson, Per and Undvall Anand, Eva and Lenshof, Andreas and Josefsson, Andreas and Welén, Karin and Bjartell, Anders and Ceder, Yvonne and Lilja, Hans and Laurell, Thomas}},
  issn         = {{1520-6882}},
  language     = {{eng}},
  number       = {{18}},
  pages        = {{6914--6921}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{Analytical Chemistry}},
  title        = {{Acoustic Enrichment of Heterogeneous Circulating Tumor Cells and Clusters from Metastatic Prostate Cancer Patients}},
  url          = {{http://dx.doi.org/10.1021/acs.analchem.3c05371}},
  doi          = {{10.1021/acs.analchem.3c05371}},
  volume       = {{96}},
  year         = {{2024}},
}