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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 ; 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.

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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
  • scopus:85191839641
  • pmid:38655666
ISSN
1520-6882
DOI
10.1021/acs.analchem.3c05371
language
English
LU publication?
yes
id
205b4eed-2e7f-45bc-9d40-7315e7d8fb55
date added to LUP
2024-04-28 11:14:19
date last changed
2024-05-15 14:31:58
@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}},
}