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  • br Introduction Immunosensors are a specific type

    2018-10-26


    Introduction Immunosensors are a specific type of biosensors and can be defined as compact analytical devices that yield measurable signals in response to specific antibody–antigen interactions. A large number of immunosensors have been developed using different kinds of transducers that exploit changes in mass, heat, electrochemical, or optical properties [1]. In particular, electrical detection technique has several advantages such as simple and convenient measurements, which enables miniaturized and inexpensive biosensors [2,3]. Carbon nanotubes (CNTs) have been widely discussed as materials with enormous potential for a wide range of in vivo and in vitro bio-applications, ranging from drug delivery to highly sensitive biosensors, owing to their superior electronic and mechanical properties along with nanoscale dimensions [4]. Significant progress has been made in exploring CNTs as electrodes and further as biosensors. Many different CNT-based sensors can be developed using the purchase eicosapentaenoic acid same approaches mentioned above for the detection of various clinically significant biomolecules. Based on the mechanism of transduction, the CNT-based immunosensors can be grouped into (1) field effect transistor (FET) immunosensors and (2) other electrochemical immunosensors such as CNT-resistors or amperometric immunosensors. DEP has been considered as a reliable, cheap and efficient CNT deposition techniques, and it purchase eicosapentaenoic acid involves the deposition of solution-dispersed CNTs between electrodes. The alignment and density of the deposited CNTs can be controlled by the AC parameters and the concentration of CNTs [5,6]. Although chemical vapor deposition (CVD) is a common method for the direct growth of CNTs or a network of CNTs, and CVD-grown CNTs have shown the best performance, DEP is generally much simpler and more cost-effective, and does not require special materials and high temperature for the growth. The analyte chosen for testing the biosensing properties of the devices is Human Arginase 1 (ARG-I or liver-type arginase), a 35kDa protein circulating in blood probably as a homotrimer. It is most abundant expressed in mammalian liver, but is also found in non-hepatic tissues, for instance red blood cells, lactating mammalian glands, and the kidney. In addition to its involvement in ammonia detoxification via the urea cycle, arginase plays a role in other processes, for instance macrophage-mediated cytotoxicity due to arginase release and inhibition of lymphocyte proliferation. It shows high activity in growing tissues, wound healing, proliferating lymphocytes and tumors. Furthermore, ARG-1 acts as a modulator of the immune response. Besides this, arginase plays a role in allergen challenged lungs, in autoimmune inflammation in the central nervous system and in acute liver injury. In plasma of healthy individuals ARG-1 is present in levels of 1.8–30ng/ml [7,8] which increases approximately 10 fold during acute phase responses. ARG-1 blood levels elevate in cancerous patients and correlate with cancer stages and poor prognosis. In particular it is detectable in peripheral blood as serum biomarker (Arg-1) for hematological malignancies, including Hodgkin\'s Lymphoma and Multiple Myeloma (MM) [9–11] and in urine as renal cell carcinoma biomarker [12]. Recent studies by quantitative urinary proteomics have also identified ARG-1 as a potential candidate molecule involved in the development of obstructive nephropathy in newborns [13]. It was shown that an elevation of arginase in a patient\'s blood is very harmful to the host immune system, more than having effect in the promotion of the tumor cell growth [14]. Typically the detection of such proteins can be performed by enzyme-linked immunosorbent assay (ELISA) which can be used in the 1 to 300ng/ml range in serum and culture supernatants [7,8,15]. In this work we describe a method to develop biosensors with high sensitivity and low cost for ARG-1 detection. One of the major challenges in the fabrication of CNT-based immunosensors is to attach antibodies or antigens to the CNTs. To do so, a molecular recognization function has to be added by a suitable functionalization that allows immobilizing the receptor on the sidewalls of the nanotubes, as we have done in the present work [16].