title: Label-free reflectometric interference microchip biosensor based on nanoporous alumina for detection of circulating tumour cells.
abstract: In this report, a label-free reflectometric interference spectroscopy (RIfS) based microchip biosensor for the detection of circulating tumour cells (CTCs) is demonstrated. Highly ordered nanoporous anodic aluminium oxide (AAO) fabricated by electrochemical anodization of aluminium foil was used as the RIfS sensing platform. Biotinylated anti-EpCAM antibody that specifically binds to human cancer cells of epithelial origin such as pancreatic cancer cells (PANC-1) was covalently attached to the AAO surface through multiple surface functionalization steps. Whole blood or phosphate buffer saline spiked with low numbers of pancreatic cancer cells were successfully detected by specially designed microfluidic device incorporating an AAO RIfS sensor, without labour intensive fluorescence labelling and/or pre-enhancement process. Our results show that the developed device is capable of selectively detecting of cancer cells, within a concentrations range of 1000-100,000 cells/mL, with a detection limit of <1000 cells/mL, a response time of <5 min and sample volume of 50 μL of. The presented RIfS method shows considerable promise for translation to a rapid and cost-effective point-of-care diagnostic device for the detection of CTCs in patients with metastatic cancer.
authors.affiliation: Ian Wark Research Institute, University of South Australia, Mawson Lakes, SA 5095, Australia; School of Chemical Engineering, University of Adelaide, SA 5005, Australia.
authors.forename: Tushar
authors.initials: T
authors.lastname: Kumeria
authors.affiliation: Ian Wark Research Institute, University of South Australia, Mawson Lakes, SA 5095, Australia; School of Chemical Engineering, University of Adelaide, SA 5005, Australia.
authors.forename: Mahaveer D
authors.initials: MD
authors.lastname: Kurkuri
authors.affiliation: Experimental Therapeutics Laboratory, Hanson Institute, Royal Adelaide Hospital, Adelaide, SA 5000, Australia; School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Kerrilyn R
authors.initials: KR
authors.lastname: Diener
authors.affiliation: Ian Wark Research Institute, University of South Australia, Mawson Lakes, SA 5095, Australia.
authors.forename: Luke
authors.initials: L
authors.lastname: Parkinson
authors.affiliation: Ian Wark Research Institute, University of South Australia, Mawson Lakes, SA 5095, Australia; School of Chemical Engineering, University of Adelaide, SA 5005, Australia. Electronic address: dusan.losic@adelaide.edu.au.
authors.forename: Dusan
authors.initials: D
authors.lastname: Losic
mesh_terms: D000537:Aluminum Oxide; D055910:Antibodies, Immobilized; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm / Q000276:immunology; D015374:Biosensing Techniques / Q000295:instrumentation*; D015815:Cell Adhesion Molecules / Q000276:immunology; D045744:Cell Line, Tumor; D000071858:Epithelial Cell Adhesion Molecule; D004867:Equipment Design; D006801:Humans; D056656:Lab-On-A-Chip Devices; D057230:Limit of Detection; D053768:Metal Nanoparticles / Q000648:ultrastructure; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation; D008855:Microscopy, Electron, Scanning; D009360:Neoplastic Cells, Circulating / Q000276:immunology / Q000473:pathology*; D016062:Porosity; D013057:Spectrum Analysis / Q000295:instrumentation; D013499:Surface Properties
chemical_list: D055910:Antibodies, Immobilized; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D000537:Aluminum Oxide