This paper describes a procedure that makes it possible to design and fabricate (including sealing) microfluidic systems in an elastomeric materialpoly(dimethylsiloxane) (PDMS)in less than 24 h. A network of microfluidic channels (with width >20 μm) is designed in a CAD program. This design is converted into a transparency by a high-resolution printer; this transparency is used as a mask in photolithography to create a master in positive relief photoresist. PDMS cast against the master yields a polymeric replica containing a network of channels. The surface of this replica, and that of a flat slab of PDMS, are oxidized in an oxygen plasma. These oxidized surfaces seal tightly and irreversibly when brought into conformal contact. Oxidized PDMS also seals irreversibly to other materials used in microfluidic systems, such as glass, silicon, silicon oxide, and oxidized polystyrene; a number of substrates for devices are, therefore, practical options. Oxidation of the PDMS has the additional advantage that it ...

Rapid prototyping of microfluidic systems in poly(dimethylsiloxane)

Hydrophilic polymers are the center of research emphasis in nanotechnology because of their perceived “intelligence”. They can be used as thin films, scaffolds, or nanoparticles in a wide range of biomedical and biological applications. Here we highlight recent developments in engineering uncrosslinked and crosslinked hydrophilic polymers for these applications. Natural, biohybrid, and synthetic hydrophilic polymers and hydrogels are analyzed and their thermodynamic responses are discussed. In addition, examples of the use of hydrogels for various therapeutic applications are given. We show how such systems’ intelligent behavior can be used in sensors, microarrays, and imaging. Finally, we outline challenges for the future in integrating hydrogels into biomedical applications.

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Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology†

When considering new sensory technologies one should look to nature for guidance. Indeed, living organisms have developed the ultimate chemical sensors. Many insects can detect chemical signals with perfect specificity and incredible sensitivity. Mammalian olfaction is based on an array of less discriminating sensors and a memorized response pattern to identify a unique odor. It is important to recognize that the extraordinary sensory performance of biological systems does not originate from a single element. In actuality, their performance is derived from a completely interactive system wherein the receptor is served by analyte delivery and removal mechanisms, selectivity is derived from receptors, and sensitivity is the result of analyte-triggered biochemical cascades. Clearly, optimal artificial sensory sys-

Conjugated polymer-based chemical sensors.

Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual's state of health. Sampling human sweat, which is rich in physiological information, could enable non-invasive monitoring. Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state. Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plastic-based sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This application could not have been realized using either of these technologies alone owing to their respective inherent limitations. The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor physical activities, and to make a real-time assessment of the physiological state of the subjects. This platform enables a wide range of personalized diagnostic and physiological monitoring applications.

/pdf/fully-integrated-wearable-sensor-arrays-for-multiplexed-in-4nphg673vl.pdf

Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

PL02-05 

All cancers are due to abnormalities in DNA. The availability of the human genome sequence has led to the proposal that resequencing of cancer genomes will reveal the full complement of somatic mutations and hence all the cancer genes. To explore the nature of the information that will be derived from cancer genome sequencing we have sequenced the coding exons of the family of 518 protein kinases, ~1.3Mb DNA per cancer sample, in 210 cancers of diverse histological types. Despite the screen being directed toward the coding regions of a gene family that has previously been strongly implicated in oncogenesis, the results indicate that the majority of somatic mutations detected are “passengers”. There is considerable variation in the number and pattern of these mutations between individual cancers, indicating substantial diversity of processes of molecular evolution between cancers. The imprints of exogenous mutagenic exposures, mutagenic treatment regimes and DNA repair defects can all be seen in the distinctive mutational signatures of individual cancers. This systematic mutation screen and others have previously yielded a number of cancer genes that are frequently mutated in one or more cancer types and which are now anticancer drug targets (for example BRAF , PIK3CA , and EGFR ). However, detailed analyses of the data from our screen additionally suggest that there exist a large number of additional “driver” mutations which are distributed across a substantial number of genes. It therefore appears that cells may be able to utilise mutations in a large repertoire of potential cancer genes to acquire the neoplastic phenotype. However, many of these genes are employed only infrequently. These findings may have implications for future anticancer drug development.

Patterns of Somatic Mutation in Human Cancer Genomes

An enhanced smart flow sensor is being developed at IMTEK in order to measure both flow and thermal properties of fluids at the same time. To be able to measure the thermal properties of a fluid, a sinusoidal voltage is applied at heater. This results in a time-dependent temperature response on a thermistor array. Amplitudes of the temperature signals on the thermistors, and thus the maximum sensitivity range of the sensor depend on the frequency of sinusoidal heating. In this report, we present the frequency response of our thermal flow sensor in nonzero flow conditions. The results are obtained via fluid-thermal coupled simulations. The frequency response shows a common low-pass characteristic of a thermal system. Full temperature amplitude is obtained up to 6 Hz while at 35 Hz 50% of the temperature amplitude remains. This can be used as a design rule for thermal gas flow sensors using a similar topology with a diaphragm.

Frequency response of a 2D flow and thermal property sensor

Miniaturized integrated thin-film biosensors were developed for use in clinical analyzers and for in vivo applications. A glucose and a lactate sensor were integrated with a pH-sensor on a flexible substrate. Both enzyme sensors are based on the electrochemical measurement of H2O2 produced by the enzymes glucoseoxidase and lactateoxidase respectively. The solid state pH-sensor uses a neutral carrier membrane. The intended application of this device is the monitoring of metabolic parameters in the intensive care unit and the operation theater and the use as a sensor module in clinical analyzers. The glucose-, lactate- and pH-sensor was tested in buffer solutions and undiluted serum showing excellent performance.

Miniaturized integrated biosensors.

We have investigated the determination of flow speed and simultaneously gas concentration in a binary gas mixture. The fabrication process and characterization of a sensor element, based on the thermal principle, is presented in this paper. The sensor is equipped with an unsymmetrical 1D-array of temperature sensors and a heater. Time modulated heating is used to extract flow speed from thermal gas properties. Phase shift determines the thermal conductivity of the gas mixture. The accurate flow velocity can be calculated from amplitude measurement afterwards. Thermal conductivity can be already determined with an accuracy of 90%.

AC characterisation of thermal flow sensor with fluid characterisation feature

This work draws attention to the optimal hierarchical nanostructure morphology and the morphological characteristics that lead to a rational design of heterogeneous nanocatalysts, especially for reactions that exhibit sluggish kinetics. A simplified methanol oxidation on two types of hierarchical nanostructures, external and internal, is reported. A complex system of asymmetric geometries was simplified by mapping 3 D geometries into 2 D models by using a mass transport approach. The macropore size was the most comprehensive characteristic to evaluate the specific activity and current density of hierarchical nanostructures. The optimal current densities for both types of nanostructures were achieved in macropore size ranges of 3.2–4.5 and 1.9–3.2 μm, respectively. The optimal mass activity of the internal nanostructures was achieved in the porosity range of 40–50 %, whereas that of the external hierarchical nanostructures was achieved at high porosity values. In comparison to internal hierarchical nanostructures, external hierarchical nanostructures tend to be cost-effective catalysts that have a high catalytic activity.

Rational Design of Morphological Characteristics to Determine the Optimal Hierarchical Nanostructures in Heterogeneous Catalysis

A system for continuous simultaneous ex vivo monitoring of blood glucose (b.g.) and subcutaneous tissue fluid glucose (s.g.) is presented. The system is based on two portable devices: (1) a continuous ambulatory blood sampler with a miniaturized thin-film glucose sensor in the sampling line and (2) a s.g. monitoring device using open tissue perfusion and measurement of glucose and conductivity for the calculation of absolute s.g. concentration. B.g. and s.g. are measured extracorporeally in a continuous manner with both devices. The system was evaluated in six healthy volunteers during an intravenous and a consecutive oral glucose tolerance test over 6 hours. >

Gerald Urban

Papers

Frequency response of a 2D flow and thermal property sensor

Miniaturized integrated biosensors.

AC characterisation of thermal flow sensor with fluid characterisation feature

Rational Design of Morphological Characteristics to Determine the Optimal Hierarchical Nanostructures in Heterogeneous Catalysis

Continuous ex vivo monitoring of glucose in blood and subcutaneous tissue fluid