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      Label-Free Microcavity Biosensors: Steps towards Personalized Medicine

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          Abstract

          Personalized medicine has the potential to improve our ability to maintain health and treat disease, while ameliorating continuously rising healthcare costs. Translation of basic research findings to clinical applications within regulatory compliance is required for personalized medicine to become the new foundation for practice of medicine. Deploying even a few of the thousands of potential diagnostic biomarkers identified each year as part of personalized treatment workflows requires clinically efficient biosensor technologies to monitor multiple biomarkers in patients in real time. This paper discusses a critical component of a regulatory system, a microcavity optical biosensor for label-free monitoring of biomolecular interactions at physiologically-relevant concentrations. While most current biosensor research focuses on improving sensitivity, this paper emphasizes other characteristics a biosensor technology requires to be practical in a clinical setting, presenting robust microcavity biosensors which are easy to manufacture and integrate with microfluidics into flexible and redesignable platforms making the microcavity biosensors deployable for continuous monitoring of biomarkers in body fluids in the clinic, in dense 2D random arrays for high-throughput applications like drug-library screening in interactomics, and of the secretory behavior of single cells in the laboratory.

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          Most cited references119

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          The path to personalized medicine.

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            Single-Molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations

            The detection of single protein molecules1,2 in blood could help identify many new diagnostic protein markers. We report an approach for detecting hundreds to thousands of individual protein molecules simultaneously that enables the detection of very low concentrations of proteins. Proteins are captured on microscopic beads and labeled with an enzyme, such that each bead has either one or zero enzyme-labeled proteins. By isolating these beads in arrays of 50-femtoliter reaction chambers, single proteins can be detected by fluorescence imaging. By singulating molecules in these arrays, ~10–20 enzymes can be detected in 100 μL (~10−19 M). Single molecule enzyme-linked immunosorbent assays (digital ELISA) based on singulation of enzyme labels enabled the detection of clinically-relevant proteins in serum at concentrations (<10−15 M) much lower than conventional ELISA3-5. Digital ELISA detected prostate specific antigen in all tested sera from patients who had undergone radical prostatectomy, down to 14 fg/mL (0.4 fM).
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              Sensitive optical biosensors for unlabeled targets: a review.

              This article reviews the recent progress in optical biosensors that use the label-free detection protocol, in which biomolecules are unlabeled or unmodified, and are detected in their natural forms. In particular, it will focus on the optical biosensors that utilize the refractive index change as the sensing transduction signal. Various optical label-free biosensing platforms will be introduced, including, but not limited to, surface plasmon resonance, interferometers, waveguides, fiber gratings, ring resonators, and photonic crystals. Emphasis will be given to the description of optical structures and their respective sensing mechanisms. Examples of detecting various types of biomolecules will be presented. Wherever possible, the sensing performance of each optical structure will be evaluated and compared in terms of sensitivity and detection limit.
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                Author and article information

                Journal
                Sensors (Basel)
                Sensors (Basel)
                Sensors (Basel, Switzerland)
                Molecular Diversity Preservation International (MDPI)
                1424-8220
                December 2012
                13 December 2012
                : 12
                : 12
                : 17262-17294
                Affiliations
                Biocomplexity Institute and Department of Physics, Indiana University, Bloomington, IN 47405, USA; E-Mail: glazier@ 123456indiana.edu
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: damarie@ 123456indiana.edu ; Tel.: +1-812-856-2537.
                Article
                sensors-12-17262
                10.3390/s121217262
                3571837
                23443397
                9c8bedfa-b639-4532-abd7-eaa52e29a64b
                © 2012 by the authors; licensee MDPI, Basel, Switzerland

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 16 November 2012
                : 10 December 2012
                : 11 December 2012
                Categories
                Article

                Biomedical engineering
                biosensors,microsensors,microcavity surface plasmon resonance,proteomics,interactomics,microfluidics,personalized medicine,biomarkers,single cell secretion

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