Direct Profiling of Cancer Biomarkers in Tumor Tissue Using a Multiplexed Nanostructured Microelectrode Integrated Circuit

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
ACS Nano (Impact Factor: 12.88). 10/2009; 3(10):3207-13. DOI: 10.1021/nn900733d
Source: PubMed


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.

Download full-text


Available from: Jeremy Squire, Mar 31, 2014
  • Source
    • "The advantage of this system over traditional microarrays is that the hybridization occurs in the liquid phase, which means that there is no need to purify the target mRNA and no wash steps are required to remove any unhybridized probes as these are not detectable, resulting in a decreased analysis time. Direct profiling of cancer biomarkers in tumor tissue using a multiplexed nanostructured microelectrode integrated circuit was recently reported by Fang et al. [17]. mRNA from tumor biopsies was analyzed for prostate cancer-related gene fusions, which could be used to distinguish between aggressive and slower progressing forms of the disease. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The development of microfluidic methodology that can be used in conjunction with drug screening and biomolecular diagnostics offers a route to evidence-based personalized medical care. Ideally, all personal diagnostics are best carried out in a rapid and frequent manner and a microfluidic interface can provide appropriate methodology. The ability to perform genetic analysis or biomarker detection at point-of-care would allow the clinician to decide on the most informed course of treatment. Microfluidic systems for biomolecular analysis at all levels, from genes to whole tissue biopsies, have been proposed. Much of the work presented here is at an early stage of development but will consider the range of design considerations together with the plethora of potential applications of integrated microfluidic technology.
    Full-text · Article · Apr 2011 · Engineering in Life Sciences
  • Source
    • "Palladium NME was constructed on a chip by electrodeposition, and modified with thiol-derivatized PNA probes for mRNA detection. The electrocatalytic signal was monitored for the hybridization events, and the current increase was observed in the presence of the complementary RNA [106]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Vast numbers of studies and developments in the nanotechnology area have been conducted and many nanomaterials have been utilized to detect cancers at early stages. Nanomaterials have unique physical, optical and electrical properties that have proven to be very useful in sensing. Quantum dots, gold nanoparticles, magnetic nanoparticles, carbon nanotubes, gold nanowires and many other materials have been developed over the years, alongside the discovery of a wide range of biomarkers to lower the detection limit of cancer biomarkers. Proteins, antibody fragments, DNA fragments, and RNA fragments are the base of cancer biomarkers and have been used as targets in cancer detection and monitoring. It is highly anticipated that in the near future, we might be able to detect cancer at a very early stage, providing a much higher chance of treatment.
    Full-text · Article · Jan 2010 · Sensors
  • Source

    Preview · Article ·
Show more