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  • br Conclusions In summary novel

    2018-11-13


    Conclusions In summary, novel SERS-active substrates were prepared by inert gas phase condensation technique using a Nanodep60 cluster deposition system. We used 2-Thienylboronic mtor inhibitor as linker or bridge molecule that attached to the silver surface on one side and to the glucose molecule on the other side. A strong Raman line was observed at 986cm in the SERS spectrum. The intensity of this line was used to quantify the d-glucose molar concentration in the range of 1μM to 500μM. A good correlation was observed between intensity of the Raman line and molar concentration of d-glucose. This result can be very significant in developing a sensor for non-invasive detection of glucose in diabetic patients using saliva samples.
    Conflict of interest
    Acknowledgements
    Introduction Cancer is a capital health problem in the modern world and therefore a major focus of modern medical research. Currently, diagnosis and disease management of most types of cancer is based on histopathological examination, combined with a molecular pathology analysis of primary tumour and potential metastatic lesions [3]. Classical molecular pathology analysis involves IHC evaluation of biomarkers that can inform on disease status and cancer subtype, as well as on molecular signatures able to guide therapy. The standard analysis is two-dimensional in the sense that the output only informs on expression intensity and pattern of the biomarker(s) in question. Nevertheless, molecular pathology assessment plays an important role in the diagnosis and disease management of several types of cancer. For example, IHC staining intensity and pattern of ErbB2/HER2 is widely used to guide treatment in human breast cancer [4,10,30]. In prostate cancer, the expression intensity and pattern of the androgen receptor (AR) is used to predict the efficacy of anti-hormonal therapy [13]. However, the informative outcome of any molecular pathology analysis depends solely on the quality of the binding reagent and the avidity of the ligand-epitope interaction in in situ, which constitutes an inherent limitation of the method. Investigating the molecular characteristics of the interaction of a given targeting reagent with a biomarker could add extra information that would aid in disease diagnosis, patient stratification, as well as in evaluation for therapy [11]. Adding to the limited repertoire of informative tumour biomarkers, we have recently described a distinct chondroitin sulfate (CS) glycosaminoglycan (GAG) modification shared between the placental and malignant tissue compartments [27]. The observation was made in our work with placental malaria, in which infected erythrocytes express the VAR2CSA protein that allows them to anchor very specifically to a distinct type of CS in the placenta, thereby avoiding immune surveillance in the spleen [6,7,28]. Interestingly this distinct type of placental-like CS (pl-CS) is present on most cancer cells as well, while absent from normal tissue except placenta. This demonstrates the status of pl-CS as a cancer specific oncofetal antigen. pl-CS can be detected in vitro, in vivo and in situ using recombinant VAR2CSA proteins (rVAR2) [27]. The pl-CS modification is broadly present across multiple tumour types and the intensity of pl-CS tissue staining correlates with progression of malignant melanoma and predicts poor recurrence-free survival in non-small cell lung cancer patients [27]. Although a promising new cancer biomarker detection-reagent, rVAR2 is subject to the same limitations of standard molecular pathology analysis as any other established biomarker reagent, lacking important information on ligand-epitope binding avidity. The Attana biosensor is an acoustic biosensor that measures changes in mass using the piezoelectric capacity of a quartz crystal (QCM technology) [17]. The change in mass per unit area on the crystal is directly proportional to the change in the crystals resonant frequency [29]. This allows for the use of the QCM technology as a microscale to measure small changes in mass, such as binding of an analyte to its immobilized ligand. More importantly, unlike surface plasmon resonance (SPR, Biacore [25,33]), which relies on the reflection of polarized light, the QCM platform is independent of the composition of the immobilized ligand. This technology therefore allows for the characterization of the binding and kinetic properties of a given analyte\'s interaction with a ligand in its native environment using fixed cells [18,23,24], and recently also live cells [16]. However, to date this has not been attempted for in situ FFPE tissue analysis of primary patient biopsies. Here, we present a method that adds a third dimension to classical two-dimensional molecular pathology assessment by incorporating a kinetic readout of analyte-ligand interactions in situ using QCM biosensor technology.