title: Capture and On-chip analysis of Melanoma Cells Using Tunable Surface Shear forces.
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(V600E) specific antibody enabled on-chip evaluation of BRAF(V600E) 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.
authors.affiliation: Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, 3084, Australia.|Department of Surgery - Austin Health, University of Melbourne, Heidelberg, Victoria, 3084, Australia.|Ludwig Institute for Cancer Research - Austin Health, Heidelberg, Victoria, 3084, Australia.
authors.forename: Simon Chang-Hao
authors.initials: SC
authors.lastname: Tsao
authors.affiliation: Centre for Personalised NanoMedicine, Australian Institute for Bioengineering and Nanotechnology, University of Queensland.
authors.forename: Ramanathan
authors.initials: R
authors.lastname: Vaidyanathan
authors.affiliation: Centre for Personalised NanoMedicine, Australian Institute for Bioengineering and Nanotechnology, University of Queensland.
authors.forename: Shuvashis
authors.initials: S
authors.lastname: Dey
authors.affiliation: Centre for Personalised NanoMedicine, Australian Institute for Bioengineering and Nanotechnology, University of Queensland.
authors.forename: Laura G
authors.initials: LG
authors.lastname: Carrascosa
authors.affiliation: Department of Surgery - Austin Health, University of Melbourne, Heidelberg, Victoria, 3084, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Christophi
authors.affiliation: Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, 3084, Australia.|School of Cancer Medicine- La Trobe University, Melbourne, Victoria, 3086, Australia.|Ludwig Institute for Cancer Research - Austin Health, Heidelberg, Victoria, 3084, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cebon
authors.affiliation: Centre for Personalised NanoMedicine, Australian Institute for Bioengineering and Nanotechnology, University of Queensland.
authors.forename: Muhammad J A
authors.initials: MJ
authors.lastname: Shiddiky
authors.affiliation: Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, 3084, Australia.|School of Cancer Medicine- La Trobe University, Melbourne, Victoria, 3086, Australia.|Ludwig Institute for Cancer Research - Austin Health, Heidelberg, Victoria, 3084, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Behren
authors.affiliation: Centre for Personalised NanoMedicine, Australian Institute for Bioengineering and Nanotechnology, University of Queensland.|School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, 4072, Australia.
authors.forename: Matt
authors.initials: M
authors.lastname: Trau
mesh_terms: D000912:Antibodies, Neoplasm / Q000737:chemistry*; D000951:Antigens, Neoplasm / Q000737:chemistry*; D045744:Cell Line, Tumor; D002469:Cell Separation / Q000295:instrumentation / Q000379:methods; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry*; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008545:Melanoma / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D011508:Chondroitin Sulfate Proteoglycans; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
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