A polymerase chain reaction for the specific detection of mycobacteria belonging to the Mycobacterium tuberculosis complex was developed. Using a single primer pair derived from the nucleotide sequence of protein antigen b of M. tuberculosis, we achieved specific amplification of a 419-base-pair DNA fragment in M. tuberculosis and M. bovis. After DNA was extracted from mycobacteria by using a simple, safe lysis procedure, we detected the 419-base-pair sequence in samples containing few mycobacteria. Preliminary data suggested that this technique could be applied to clinical specimens for early and specific diagnosis of tuberculosis.

The reference point method was found to be tractable for trading-off between deviations from ideal values of all the criteria. Some criteria computations are based on dynamic programs with value iteration whose run time can be bounded by a low-degree polynomial. For designing standard PCR primers, the scheme offers in a relative gain in computing speed of up to 50: 1 over ad-hoc computational methods. Single PCR primer pairs have been used as model systems in order to simplify the quantization of the computational acceleration factors. The program has been structured so as to facilitate the analysis of large numbers of primer pairs with minor modifications. The scheme significantly increases primer design throughput which in turn facilitates the use of oligonucleotides in a wide range of applications including: multiplex PCR and other nucleic acid-based amplification systems, as well as in zip code targeting, oligonucleotide microarrays and nucleic acid-based nanoengineering.

Biotinylated glycoconjugates which were designed as oligosaccharides attached to 30 kDa polyacrylamide were coated on a microarray platform XNAonGOLD, which was developed earlier for an oligonucleotide assay. The specificity of antibodies to carbohydrate antigens was analyzed using the glyco-microarray. Comparison of the obtained results with those of common 96-well plate ELISA completely coincided with the found antibody specificities. However, parameters such as the analytical sensitivity of the method and the amount of biotinylated material coated on the microarray platform proved to be worse than expected.

Motivated by recent experiments, where a voltage biased Josephson junction is placed in series with a resonator, the classical dynamics of the circuit is studied in various domains of parameter space. This problem can be mapped onto the dissipative motion of a single degree of freedom in a nonlinear time-dependent potential, where in contrast to conventional settings the nonlinearity appears in the driving while the static potential is purely harmonic. For long times the system approaches steady states which are analyzed in the underdamped regime over the full range of driving parameters including the fundamental resonance as well as higher and sub-harmonics. Observables such as the dc-Josephson current and the radiated microwave power give direct information about the underlying dynamics covering phenomena as bifurcations, irregular motion, up-and down conversion. Due to their tunability, present and future set-ups provide versatile platforms to explore the changeover from linear response to strongly nonlinear behavior in driven dissipative systems under well defined conditions. I. INTRODUCTIONThe nonlinear properties of Josephson junctions (JJs) have made such devices a key circuit element for classical and quantum electronics. Accordingly, there has been a long tradition of studying non-linear phenomena in driven superconducting circuits, starting as early as the 1960s with the discovery of Shapiro steps 1 . While Shapiro-steps have remained a tool in exploring new directions in Josephson physics, for instance in atomic point contacts 2-6 , other nonlinear phenomena, like synchronization, have been investigated in arrays of JJs: as a test-bed for generic theory models to capture synchronization phenomena 7,8 , but as importantly with the prospect of applications as sources of more intense coherent radiation 9 , cf. also new developments using intrinsic arrays 10-12 .More recently, the nonlinearity of the JJ was exploited as the crucial factor in enabling the high sensitivity of Josephson bifurcation amplifiers, achieving substantial improvements towards reaching quantum-limited measurement processes [13][14][15][16] . Most of the features of Josephson bifurcation amplifiers, in fact, only rely on (and can consequently be described by) any type of nonlinearity 17-22 , e.g., Duffing-type models, so that only recently the full nonlinear potential of the JJ has become of interest in this field 23 .A recent addition to the field of driven nonlinear JJs 24-26 are experiments on a dc-biased JJ connected to a resonator 27-29 . In this sort of setup, charge transfer through the JJ leads to excitations in the resonator, and therefore allows to convert energy carried by charge quanta into quantum microwave photons. In these devices measurement of both the Josephson current and the emitted microwave radiation is possible, a distinct advantage in comparison to other recently proposed transport setups 30,31 , which show similar nonlinear features like bifurcations, period multiplication and up-and downconversion 32-34 . S...

A flow injection thermal microbiosensor was designed for the simultaneous determination of multiple analytes. The biosensor consisted of five thin-film thermistors which were located along a single microchannel. The device was fabricated on a quartz chip by micromachining. The feasibility of employing this system for the detection of two independent enzyme reactions was demonstrated using two different pairs of enzymes, urease-penicillinase and urease-glucose oxidase. The enzymes were immobilized on agarose beads, which were then sequentially packed into distinct regions of the microchannel. Using this method, samples containing urea mixed with penicillin V or with glucose were simultaneously analysed. Linear ranges of up to 20 mmol l-1 urea, 40 mmol l-1 penicillin V and 8 mmol l-1 glucose (saturated with 02) were obtained using a flow rate of 30 p1 min-1 and a sample volume of 20 pl. The relative standard deviations for urea and penicillin V assays were 1.13 and 2.42% for the first 100 samples and 1.17 and 2.78% for 200 samples, respectively. The sensor is capable of analysing 25 samples per hour.