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Capture and On-chip analysis of Melanoma Cells Using Tunable Surface Shear forces

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posted on 2022-12-20, 23:51 authored by SC-H Tsao, R Vaidyanathan, S Dey, LG Carrascosa, C Christophi, Jonathan CebonJonathan Cebon, MJA Shiddiky, Andreas BehrenAndreas Behren, M Trau
With new systemic therapies becoming available for metastatic melanoma such as BRAF and PD-1 inhibitors, there is an increasing demand for methods to assist with treatment selection and response monitoring. Quantification and characterisation of circulating melanoma cells (CMCs) has been regarded as an excellent non-invasive candidate but a sensitive and efficient tool to do these is lacking. Herein we demonstrate a microfluidic approach for melanoma cell capture and subsequent on-chip evaluation of BRAF mutation status. Our approach utilizes a recently discovered alternating current electrohydrodynamic (AC-EHD)-induced surface shear forces, referred to as nanoshearing. A key feature of nanoshearing is the ability to agitate fluid to encourage contact with surface-bound antibody for the cell capture whilst removing nonspecific cells from the surface. By adjusting the AC-EHD force to match the binding affinity of antibodies against the melanoma-associated chondroitin sulphate proteoglycan (MCSP), a commonly expressed melanoma antigen, this platform achieved an average recovery of 84.7% from biological samples. Subsequent staining with anti-BRAF V600E specific antibody enabled on-chip evaluation of BRAFV600E mutation status in melanoma cells. We believe that the ability of nanoshearing-based capture to enumerate melanoma cells and subsequent on-chip characterisation has the potential as a rapid screening tool while making treatment decisions.

Funding

This work was supported by the NHMRC CDF (APP1088966) and ARC DECRA (DE120102503). Although not directly involved in this work, our lab is receiving support from the National Breast Cancer Foundation of Australia (CG-12-07). This grant has significantly contributed to the environment to stimulate the research described here. We would also like to acknowledge the Victorian State Government Operational Infrastructure Support Program for partial funding of the parts of the project based at the Olivia Newton-John Cancer Research Institute. S.C.T is funded by the Australia Postgraduate Award and the Australasian College of Surgeons Foundation for Surgery ANZ journal of Surgery research scholarship.

History

Publication Date

2016-01-27

Journal

Scientific Reports

Volume

6

Issue

1

Article Number

19709

Pagination

10p.

Publisher

Nature Publishing Group

ISSN

2045-2322

Rights Statement

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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