HER2 Protein Biomarker Based Sensor Systems for Breast Cancer Diagnosis

that can be used as a diagnostic tool for the detection HER2 protein and monitoring the progression of other disease in a low-cost sensing setup. It is also anticipated that the developed sensing system can be handled by non-professional personals in a diagnostic laboratory [19]. The biosensor technology has also been significantly applied for the targeting and imaging of human HER2 expressing cells and tumors. A new class of engineered diagnostic molecule “affibody”developed by a Swedish biotechnology company, “Affibody AB” has been applied to develop a nanoprobe for the diagnosis of HER2-expressing tumor and cell imaging [20]. The nanoprobes were designed by linking the N-terminus cysteine residue accurately conjugated with maleimidefunctionalized nanoparticles to make nanoparticle-affibody conjugates. It this system near-infrared quantum dots and iron oxide nanoparticles as two representative nanomaterials were used. The in vitro and in vivo study clearly indicated the promise of this nano-conjugate for the quick and selective diagnosis of HER2 expressing cells. In the same year a Piezoelectric Microcantilever Sensor (PEMS) was reported by an American research group lead by Gregory et al. [21,22]. His group successfully demonstrated the detection of both recombinant and naturally occurring HER2 levels (>2 ng/mL) in the serum of breast cancer patients. Another piezoelectric sensor was developed for the realtime, label-free, in situ detection of HER2 protein in diluted serum using the first longitudinal extension mode of a lead Zirconate-Lead Titanate (PZT)/glass PEMS with H3 single-chain Variable Fragment (scFv) immobilized on the 3-mercaptopropyltrimethoxysilane insulation layer of the PEMS surface. The linear detection range of HER2 was between the concentrations of 6–60 ng/ml in a diluted human serum [22]. A newly explored nanomaterial, graphene has also been explored for the development of biosensor for the detection of HER2 protein. In this regard, recently and Graphene-Encapsulated Nanoparticles (GEN) has been developed for the selective detection of HER2 [23]. It this case, a novel 2 dimensional GEN was used which significantly increased the electrical conductivity, mechanical flexibility, surface area, chemical and thermal stability of the biosensor for the highly selective detection of HER2 protein with the detection limit of 1pM. Until the start of year 2013, most of the biosensor readout devices were based on antibodies and a very few was based on affibody. Since these detection molecules are chemically protein in nature, hence the stability and long term storage of biosensor based on these molecules is critical. To overcome these critical issues, very recently an aptamer based biosensor was