Acoustic Enrichment of Heterogeneous Circulating Tumor Cells and Clusters from Metastatic Prostate Cancer Patients
(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)
- author
- Magnusson, Cecilia LU ; Augustsson, Per LU ; Undvall Anand, Eva LU ; Lenshof, Andreas LU ; Josefsson, Andreas ; Welén, Karin ; Bjartell, Anders LU ; Ceder, Yvonne LU ; Lilja, Hans LU and Laurell, Thomas LU
- organization
-
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- LU Profile Area: Light and Materials
- LTH Profile Area: Nanoscience and Semiconductor Technology
- LTH Profile Area: Engineering Health
- NanoLund: Centre for Nanoscience
- Acoustofluidics group (research group)
- Clinical Chemistry, Malmö (research group)
- LTH Profile Area: Photon Science and Technology
- LUCC: Lund University Cancer Centre
- eSSENCE: The e-Science Collaboration
- Urological cancer, Malmö (research group)
- EpiHealth: Epidemiology for Health
- Medical Molecular Biology (research group)
- SEBRA Sepsis and Bacterial Resistance Alliance (research group)
- publishing date
- 2024-04
- 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
- 2024-07-08 11:38:09
@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}}, }