title: Direct profiling of cancer biomarkers in tumor tissue using a multiplexed nanostructured microelectrode integrated circuit.
abstract: The analysis of panels of nucleic acid biomarkers offers valuable diagnostic and prognostic information for cancer management. A cost-effective, highly sensitive electronic chip would offer an ideal platform for clinical biomarker readout and would have maximal utility if it was (i) multiplexed, enabling on-chip assays of multiple biomarkers, and (ii) able to perform direct (PCR-free) readout of disease-related genes. Here we report a chip onto which we integrate novel nanostructured microelectrodes and with which we directly detect cancer biomarkers in heterogeneous biological samples-both cell extracts and tumor tissues. Coarse photolithographic microfabrication defines a multiplexed sensing array; bottom-up fabrication of nanostructured microelectrodes then provides sensing elements. We analyzed a panel of mRNA samples for prostate cancer related gene fusions using the chip. We accurately identified gene fusions that correlate with aggressive prostate cancer and distinguished these from fusions associated with slower-progressing forms of the disease. The multiplexed nanostructured microelectrode integrated circuit reported herein provides direct, amplification-free, sample-to-answer in under 1 h using the 10 ng of mRNA readily available in biopsy samples.
authors.affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Fang
authors.forename: Leyla
authors.initials: L
authors.lastname: Soleymani
authors.forename: Georgios
authors.initials: G
authors.lastname: Pampalakis
authors.forename: Maisa
authors.initials: M
authors.lastname: Yoshimoto
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Squire
authors.forename: Edward H
authors.initials: EH
authors.lastname: Sargent
authors.forename: Shana O
authors.initials: SO
authors.lastname: Kelley
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D045744:Cell Line, Tumor; D004247:DNA / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008839:Microelectrodes; D049329:Nanostructures / Q000737:chemistry*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis / Q000295:instrumentation*; D012313:RNA / Q000032:analysis / Q000737:chemistry / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D012313:RNA; D004247:DNA