Capture and on-chip analysis of melanoma cells using tunable surface shear forces

Tsao, Simon Chang-Hao, Vaidyanathan, Ramanathan, Dey, Shuvashis, Carrascosa, Laura G., Christophi, Christopher, Cebon, Jonathan, Shiddiky, Muhammad J. A., Behren, Andreas and Trau, Matt (2016) Capture and on-chip analysis of melanoma cells using tunable surface shear forces. Scientific Reports, 6 19709.1-19709.10. doi:10.1038/srep19709


Author Tsao, Simon Chang-Hao
Vaidyanathan, Ramanathan
Dey, Shuvashis
Carrascosa, Laura G.
Christophi, Christopher
Cebon, Jonathan
Shiddiky, Muhammad J. A.
Behren, Andreas
Trau, Matt
Title Capture and on-chip analysis of melanoma cells using tunable surface shear forces
Formatted title
Capture and on-chip analysis of melanoma cells using tunable surface shear forces
Journal name Scientific Reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2016-01-27
Sub-type Article (original research)
DOI 10.1038/srep19709
Open Access Status DOI
Volume 6
Start page 19709.1
End page 19709.10
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing
Language eng
Subject 1000 General
Abstract 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 specific antibody enabled on-chip evaluation of BRAF 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.
Formatted abstract
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-BRAFV600E 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in Thomson Reuters Web of Science Article
Scopus Citation Count Cited 0 times in Scopus Article
Google Scholar Search Google Scholar
Created: Fri, 29 Jan 2016, 23:37:47 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences