Fast-scan cyclic voltammetry (FSCV) is applied to the tip of a scanning electrochemical microscope (SECM) for imaging the distribution of chemical species near a substrate. This approach was used to image the diffusion layer of both a large substrate electrode (3-mm-diameter glassy carbon) and a microelectrode substrate (10-microm-diameter Pt). Additionally, oxygen depletion near living cells was measured and correlated to respiratory activity. Finally, oxygen and hydrogen peroxide were simultaneously detected during the oxidative burst of a zymosan-stimulated macrophage cell. These results demonstrate the utility of FSCV-SECM for chemical imaging when conditions are chosen such that feedback interactions with the substrate are minimal.

Fast-scan cyclic voltammetry at scan rates between 5 and 1000 Vs −1 was performed at the tip of a scanning electrochemical microscope immersed in a solution of redox mediator. The effect of conducting and insulating substrates on the voltammetric signal was investigated as a function of scan rate and tip-substrate distance. It was found that diffusional interactions between the tip and the substrate are greatest at lower scan rates and on the reverse sweep of the voltammogram. At the fastest scan rates used, the tip could be brought to with 1 μm of the substrate without appreciable perturbation of the voltammogram. By selecting scan rates and tip-substrate distances such that feedback effects were negligible, it was possible to image the diffusion layer of a 10 μm Pt substrate electrode. With the tip placed 1 μm above a biological cell, tip-substrate diffusional interactions were greatly diminished at a scan rate of 100 Vs −1 , and absent at a scan rate of 1000 Vs −1 . These results suggest conditions can be selected that allow chemical imaging of substrates without the feedback interactions typically encountered in scanning electrochemical microscopy.

The HER2 gene, amplified in 10 to 35% of invasive human breast carcinomas, has prognostic and therapeutic implications. Fluorescent in situ hybridization is one method currently used for assessing HER2 status, but fluorescent in situ hybridization involves the time-consuming step of manual signal enumeration. To address this issue , Vysis has developed an automated signal enumeration system , Vysis AutoVysion. A multicenter , blinded study was conducted on 39 formalin-fixed , paraffin-embedded invasive breast carcinoma specimens , including 20 HER2 nonamplified and 19 HER2 amplified (weakly to highly amplified) , provided in duplicate to each study site for analysis. Calculation of the HER2/CEP17 ratio and the hands-on time of both manual and automated enumeration approaches were compared. Overall agreement of HER2 classification results (positive and negative) was 92.5% ( The HER2 gene (ERBB2) is located on chromosome 17 (q11.2-q12) and encodes a 185-kd transmembrane glycoprotein with intracellular tyrosine kinase activity, which is closely related to the epidermal growth factor receptor.1-6 Overexpression of the HER2 oncogene seems to stimulate growth and cellular motility and has been implicated in several malignancies. 4,6,7 Approximately 10 to 35% of invasive human breast carcinomas are associated with HER2 protein overexpression.2,6,8 HER2 overexpression is considered an unfavorable prognostic factor and is associated with better response rates to trastuzumab (Herceptin) therapy and anthracycline-based chemotherapy regimens. 9 Most breast carcinomas that overexpress HER2 are invasive ductal adenocarcinomas (95.5%) and are high-grade tumors [histopathological grades 2 (28%) or 3 (69%)]. Overexpression of HER2 is rare in invasive lobular carcinoma (0.8%) and other specialized types of breast carcinomas. 8,10 Studies have shown that the most common mechanism (90 to 96%) of HER2 overexpression is gene amplification. 2,9,11,12 Widely used approaches to assess HER2 status include immunohistochemistry (IHC) to determine protein expression and fluorescent in situ hybridization (FISH) to determine HER2 gene copy number. 4,11,[13][14][15] Reportedly, FISH has shown greater interlaboratory concordance and has been found to be a better predictor of response to trastuzumab (Herceptin) therapy, as compared with IHC.