Biomedical subjects

I Freund

Publications and source records attributed to I Freund.

At least 19 recordsLinked to original sources

PubMed2001

Multiparametric microsensor chips for screening applications.

The identification of drug targets for pharmaceutical screening can be greatly accelerated by gene databases and expression studies. The identification of leading compounds from growing libraries is realized by high throughput screening platforms. Subsequently, for optimization and validation of identified leading compounds studies of their functionality have to be carried out, and just these functionality tests are a limiting factor. A rigorous preselection of identified compounds by in vitro cellular screening is necessary prior to using the drug candidates for the further time consuming and expensive stage, e.g. in animal models. Our efforts are focused to the parallel development, adaptation and integration of different microelectronic sensors into miniaturized biochips for a multiparametric, functional on-line analysis of living cells in physiologically environments. Parallel and on-line acquisition of data related to different cellular targets is required for advanced stages of drug screening and for economizing animal tests.

Biocompatible Materials↗

PubMed2001

Simultaneous measurement of cellular respiration and acidification with a single CMOS ISFET.

In vivo, the pH value and oxygen partial pressure are the most important physico-chemical parameters in the microenvironment of human tissues. In vitro, the extracellular acidification rate of cell cultures is an indicator of global cellular metabolism, while the rate of oxygen consumption is a measure of mitochondrial activity. Earlier approaches had the disadvantage that these two values had to be measured with two separate sensors at different loci within the tissue or cell culture. Furthermore, conventional Clark-type oxygen sensors are not very compatible for miniaturisation, making it impossible to measure at small cell volumes or even at the single cell level. We have, therefore, developed an ISFET based sensor structure which is able to measure both pH and oxygen partial pressure. This sensor structure was tested in vitro for simultaneous records of cellular acidification and respiration rates at the same site within the cell culture. This sensor is manufactured by a CMOS-process.

Biosensing Techniques↗

PubMed2001

Approach to a multiparametric sensor-chip-based tumor chemosensitivity assay.

Although not widely practiced by oncologists, in vitro tumor chemosensitivity assays (TCA) have proved to increase the lifetime of tumor patients in prospective clinical trials. By individualizing cancer therapy, they can support the clinician's decision which is usually based on empirically retrieved data and thereby prevent inadequate chemotherapy. We present the first results of a new sensor-chip-based technology which might be useful for a multiparametric TCA. In particular, the aspect of dynamic on-line data generation on intact cellular specimens is a major difference to alternative assays. A series of experiments has been performed on cell lines and human tumor explants. Cell cultures and tumor tissue explants were placed on miniaturized silicon and glass sensor chips. The sensor data currently analyze metabolic profiles (rates of extracellular acidification and cellular oxygen consumption) and changes in cell morphology (monitoring of electric impedance). With the cell lines, drug-associated cellular signals have been detected with all three parameters, while primary explants so far caused metabolic responses only. In particular, cellular respiration or mitochondrial activity seems to be a most sensitive indicator of acute cytotoxic effects. The experimental results were achieved using different test versions. Besides giving a status report, the theoretical potential and current problems of sensor chip technology in TCA is discussed.

Acetaldehyde↗

PubMed2001

[Immunisation of fancy chickens against Newcastle disease].

The German Regulation on Fowl plague which is in force since 1994 laid down that any chicken of all races and all hybrids must be vaccinated against Newcastle disease (ND) in a mode that an adequate immunity is achieved. Onset, duration, and resistance to challenge of immunity induced by vaccination is well documented in the scientific literature for hybrid chicken of the layer and meat types. These data prove also innocuity and efficacy of the registered vaccines. In contrast, only a few and incomplete data exist on the development of ND directed immunity in fancy chickens. The present study describes vaccinations of chickens of 14 different hobby breeds with live LaSota vaccine (conjunctival application of 10(6) embryo-infective dose50 per bird) and with an inactivated oil-emulsion vaccine (intramuscular application of 0.5 ml per bird) and subsequent intramuscular challenge infections using the highly virulent NDV strain Herts 33/66. Chickens of all 14 breeds tolerated the application of both vaccines. All fancy chickens reacted with the production of serum antibodies which were measured in the haemagglutination inhibition (HI) and virus neutralisation (VN) tests. According to the scientific literature, maximal antibody levels are reached in hybrid chickens between day 10 and 20 post vaccination. In contrast, in fancy chickens the antibody maxima are delayed to the seventh to eighth week post vaccination. All fancy chickens vaccinated either once with live LaSota virus or with live and inactivated vaccines resisted challenge with the highly virulent Herts 33/66 strain of NDV and did not develop any signs of disease. There are indications for gradual differences in susceptibility of different breeds of fancy chickens. The levels of non-specific neutralisation as measured in the virus neutralisation test differ between breed. Also, the viral content in tissues obtained from non-vaccinated but challenged birds differ markedly. It is concluded from the results of this study that fancy chickens can also successfully protected against Newcastle disease by using live and inactivated vaccines which are licensed for hybrid chickens. However, the optimal time for the detection of maximal antibody levels in fancy chickens is reached seven to eight weeks post vaccination.

Animals↗

PubMed2000

Non-invasive measurement of cell membrane associated proton gradients by ion-sensitive field effect transistor arrays for microphysiological and bioelectronical applications.

The pH in the cellular microenvironment (pH(M)) is an important regulator of cell-to-cell and cell-to-host interactions. Additionally the extracellular acidification rate of a cell culture is an important indicator of global cellular metabolism. In a new approach a biocompatible ion-sensitive field effect transistor (ISFET)-array was developed to measure the pH(M) close to a surface and the global extracellular acidification rate at the same time. This ISFET-array is part of a new multiparametric microsensor chip. The paper highlights some basic applications of this method for in-vitro measurements. Using a fluid perfusion system for cell culture media, it is possible to measure the pH(M) of few (five to ten) adherent tumor cells in a distance of 10-100 nm from the cell plasma membrane. Experiments showed a pH(M)-value of 6.68 +/- 0.06 pH. Further experiments suggest that both the low pH, and the extracellular acidification rate of the examined tumor cell line are mainly built up by glycolysis.

Biosensing Techniques↗

PubMed2000

Higher-order extrema in two-dimensional wave fields.

Higher-order extrema with topological indices greater than unity are discussed. Explicit constructions are given for their wave functions, and simple geometric rules are presented for analysis of their topological indices. Experimental means for verifying the theory with use of Gaussian laser beams are considered, unusual properties of optical vortices constructed from this new type of critical point are described, and applications to topologically based optical arithmetic are suggested.

Models, Theoretical↗

PubMed1998