Quantitative measurement of human anti-HCV Core immunoglobulins on an electrical biochip platform.

The importance of early diagnosis devices increased continuously in the last two decades and plays an important role in medical care. Early stage diagnosis of e.g. ovarian cancer, HCV-infection or HIV-infection increased the survival rate of patients significantly. In parallel there is a trend leaving centralized diagnostic laboratories in order to get closer to the patient to perform analysis of even complex parameters in the field. This often saves time, increases the prognosis of the patient significantly and is cheaper in many cases. In this study we employ a rapid and cost-effective detection system based on electrical biochip technology for decentralized detection of anti-HCV Core immunoglobulins (HCV antibodies). In this system the qualitative and quantitative detection of virus-specific antibodies is done by an ELISA directly on a gold electrode array utilizing HCV Core as capture antigen. The biochip allows antibody detection within 20 min. Signal amplification was done by enzyme labelling and by "Single Electrode Redox Cycling". This method enhances current signals up to 40-fold in comparison to simple oxidation. The sensitivity of this approach is therefore comparable to a standard microtiter plate based ELISA with a 9-fold saving of assay time. This biochip system allows serum or whole blood analysis with no signal loss or increasing background caused by the red blood cells. Fields of application can be hospital emergency units where only single detections have to be conducted in a quick manner or by the general practitioner.

Electrical protein array chips for the detection of staphylococcal virulence factors.

A new approach for the detection of virulence factors of Staphylococcus aureus and Staphylococcus epidermidis using an electrical protein array chip technology is presented. The procedure is based on an enzyme-linked sandwich immunoassay, which includes recognition and binding of virulence factors by specific capture and detection antibodies. Detection of antibody-bound virulence factors is achieved by measuring the electrical current generated by redox recycling of an enzymatically released substance. The current (measured in nanoampere) corresponds to the amount of the target molecule in the analyzed sample. The electrical protein chip allows for a fast detection of Staphylococcus enterotoxin B (SEB) of S. aureus and immunodominant antigen A homologue (IsaA homologue) of S. epidermidis in different liquid matrices. The S. aureus SEB virulence factor could be detected in minimal medium, milk, and urine in a concentration of 1 ng/ml within less than 23 min. Furthermore, a simultaneous detection of SEB of S. aureus and IsaA homologue of S. epidermidis in a single assay could be demonstrated.

Computer-aided continuous drug infusion: setup and test of a mobile closed-loop system for the continuous automated infusion of insulin.

For a diabetes mellitus patient, tight control of glucose level is essential. Results are reported of an investigation of the suitability of existing wearable continuous insulin infusors controlled and adjusted by a control algorithm using continuous glucose measurements as input to perform the functionality of an artificial pancreas. Special attention was given to the development of a continuous glucose monitor and to evaluate which quality of input data is necessary for the control algorithm. In clinical trials, it was found that for patients in a controlled environment an autonomously regulating control algorithm leads to an improved adjustment of patient glucose values and less overall insulin infusion as compared with the best fixed preprogrammed insulin infusion profiles of standard pump therapy. For the limited number of cases studied here, functionality of the control algorithm could tolerate some delay between the actual glucose values in the patient interstitial fluid and the algorithm input of up to 30 min. A quasicontinuous glucose measurement delivering actual glucose values every 5-10 min seems to be suited to control an artificial pancreas.

Electrical biochip technology--a tool for microarrays and continuous monitoring.

Based on electrical biochips made in Si-technology cost effective portable devices have been constructed for field applications and point of care diagnosis. These miniaturized amperometric biosensor devices enable the evaluation of biomolecular interactions by measuring the redox recycling of ELISA products, as well as the electrical monitoring of metabolites. The highly sensitive redox recycling is facilitated by interdigitated ultramicroelectrodes of high spatial resolution. The application of these electrical biochips as DNA microarrays for the molecular diagnosis of viral infections demonstrates the measurement procedure. Self-assembling of capture oligonucleotides via thiol-gold coupling has been used to construct the DNA interface on-chip. Another application for this electrical detection principle is continuous measuring with bead-based biosensors. Here, paramagnetic nanoparticles are used as carriers of the bioanalytical interface in ELISA format. A Si-micromachined glucose sensor for continuous monitoring in interstitial fluid ex vivo shows the flexibility of the electrical platform. Here the novel approach is a pore membrane in micrometer-dimensions acting as a diffusion barrier. The electrochemical detection takes place in a cavity containing glucose oxidase and a Pt-electrode surface. The common hydrogen peroxide detection, together with Si technology, enable precise differential measurements using a second cavity.