biomarker melanoma chip

The incidence of melanoma, has risen dramatically during the past decades, surpassing other cancers. While the available diagnostic measures are largely limited to clinical and histological criteria with poor prognostic value, the development of serum markers provides an opportunity for early detection of progressive disease and thus for the reduction of later burdens, cost and suffering, of grave late stage illness. The proposed melanoma biomarker chip holds major potential for preventing or reducing costs on therapies and medication and is extremely useful in drug development for predicting drug efficacy and reviewing drugs toxicity, thus enhancing the success rate and reducing the time and costs of drug development, which is of great interest for health insurance companies and pharma industry respectively. The challenge is to develop a protein biomarker chip for diagnosis of melanoma that is robust, sensitive, easy to use, and cost-effective. Technical improvement of protein chip surfaces is important to extend the biochip protein methodology to clinical diagnostics and improve detection limits in clinical samples. Although different biochip platforms are already available, the level of sensitivity obtainable is limited and in contrast to DNA-chip platforms protein chip platforms are still in their infancy. Herein, we propose chip formats that overcome these limitations, formats that represent the whole range of binding chemistries (adsorption, covalent, electrostatic binding; complexation; affinity) to select the very best surfaces for the biomarker chip. Apart from previously developed and commercial chip surfaces platforms made of hydrogels based on poly(vinyl alcohol) and polyurethane, and porous polysaccharide-doped sol-gels that at the same time provide a quasi-liquid, swelling environment for protein immobilization and are mechanically stable and highly reactive will be developed. Furthermore, porous reactive methacrylates developed by photografting using photoinduced living graft copolymerization as well as Cu2+ chelating matrices for protein complexation and SH- modified oligonucleotides or ssDNA for site-specific DNA-directed protein immobilization. The chip surfaces will be characterized by optical profilometry and AFM. The interaction between the chip surface and the protein will be studied by molcular modelling. The biomarkers to be used in these studies include the known serum markers S100, MIA, MERV and VEGF and novel serum biomarkers derived from the literature and ongoing SELDI-TOF screening of biomarker proteins in sera from melanoma patients. The crossreactivity of antibodies - defined as tendency to bind to several structurally related analytes - will be accounted for by use of multivariate calibration algorithms and chemometrics.