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Gold nanoparticles (AuNPs) provide excellent platforms for the development of colorimetric biosensors as they can be easily functionalised, displaying different colours depending on their size, shape and state of aggregation. In the last decade, a variety of biosensors have been developed to exploit the extent of colour changes as nano-particles (NPs) either aggregate or disperse, in the presence of analytes. Of critical importance to the design of these methods is that the behaviour of the systems has to be reproducible and predictable. Much has been accomplished in understanding the interactions between a variety of substrates and AuNPs, and how these interactions can be harnessed as colorimetric reporters in biosensors. However, despite these developments, only a few biosensors have been used in practice for the detection of analytes in biological samples. The transition from proof of concept to market biosensors requires extensive long-term reliability and shelf life testing, and modification of protocols and design features to make them safe and easy to use by the population at large. Developments in the next decade will see the adoption of user friendly biosensors for point-of-care and medical diagnosis as innovations are brought to improve the analytical performances and usability of the current designs. This review discusses the mechanisms, strategies, recent advances and perspectives for the use of AuNPs as colorimetric biosensors.

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SummaryResting autoreactive T cells are present in the circulation ofnormal individuals without pathologic consequences . In autoimmune animal models, stimulation of these self-reactive T cells in the presence of costimulatory molecules B7-1 results in T cell-mediated autoimmune disease, whereas B7-2 stimulation generates regulatory autoreactive T cells that abrogate disease severity . Thus, reactivation in the brain of myelin-autoreactive T cells by antigen with costimulatory molecules may be a critical event in the pathophysiology of multiple sclerosis (MS), a putative autoimmune disease of central nervous system (CNS) myelin. We investigated the expression of cytokines and costimulatory molecules in a panel of 41 histologically characterized CNS specimens from 15 MS and 10 control cases using semiquantitative reverse transcriptase-polymerase chain reaction and immunocytochemistry . In four cases, vascular CNS infarcts with inflammation were compared with MS plaques from the same brain. We observed increased expression ofB7-1 and interleukin (IL) 12p40 in acute MS plaques, particularly from early disease cases but not in inflammatory infarcts. B7-1 staining was localized predominantly to the lymphocytes in perivenular inflammatory cuffs but not the parenchyma. In contrast, B7-2 was expressed predominantly on macrophages both in MS lesions ofvaried time duration and in inflammatory infarcts. These findings indicate that an early event in the initiation ofMS involves upregulation o£ B7-1 and IL-12, resulting in conditions that maximally stimulate T cell activation and induction of T helper 1-type immune responses .A utoimmune disease is presumably mediated by activated, autoantigen-reactive T cells (1-8) . Two distinct signals are required to induce differentiation of naive to activated, effector T cells : an antigen-specific signal mediated through the T cell receptor, and a second non-antigenspecific "costimulatory" signal (9, 10) . Interactions between CD28 and its counterreceptors, B7-1 (CD80) and B7-2 (CD86), are important T cell-costimulatory signals (11, 12) . Essentially all CD4 + and most CD8+ T cells express CD28 constitutively, and CD28-deficient T cells show a markedly reduced response to antigen stimulation (13) . A second ligand for B7 is CTLA-4, which is expressed on T cells after activation (14) and also may regulate T cell function (15) . The B7 molecules regulate IL-2 secretion and costimulate T cell proliferation (16)(17)(18) . Blocking of the B7-CD28 pathway in vitro results in T cell anergy (19-21) whereas in vivo blocking of the B7-CD28 pathway results in immunosuppression (22)(23)(24) .Aberrant expression of B7-costimulatory molecules is important in experimental autoimmune diabetes . Doubletransgenic mice with T cell receptors recognizing a viral antigen expressed on pancreatic islet cells do not develop diabetes . Triple-transgenic mice that additionally expressed B7-1 on pancreatic islet cells, however, developed massive tissue destruction and diabetes (25) . Moreover, double transgeni...