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

A novel microphysiometry platform for dynamic cell culture monitoring in drug screening and cancer cell research is presented. The transparent system features an integrated cell cultivation area, microfluidics and (bio-)sensors for multiparametric metabolic monitoring, combined on a single glass chip. The parameters include glucose and lactate (amperometric biosensors), oxygen (amperometric), pH (potentiometric) and cellular adhesion (interdigital electrode). In contrast to traditional silicon chip based systems, the choice of transparent materials allows microscopy at all times of cell cultivation and measurement. The introduction of biosensors allows the monitoring of additional key metabolic parameters with a detection limit for lactate as low as 2 µM. Integrated multi layer microfluidics enable dynamic measurements, further improving the analytical performance. The modular system is microfabricated in a cost-effective hybrid integration of thin film and laminate technology.

A novel multiparametric microphysiometry system for dynamic cell culture monitoring

We present a novel approach to produce a micromachined low cost hotplate gas sensor with reduced number of technology steps. The basic idea was to realize a simple device on common silicon substrates using conventional photolithography, sputtering and evaporation techniques. Two main performance parameters were targeted: the power consumption should not exceed 200 mW for an operation at 350 degree(s)C-400 degree(s)C and the thermal response time should be faster than 1 second. Fast thermal time constants allows the operation of device in temperature pulse mode. The first step of the development was the theoretical determination of the power consumption of the micromachined substrates, even temperature distribution on the sensitive area and sufficient mechanical stability. For this we build models describing the thermal behavior of the devices by means of the finite element method (FEM) and corresponding resistance-capacitor-networks (RC-network). Then we developed technological processes to fabricate sensor structures according to the optimal geometry resulting from the model calculations. A first prototype is introduced in this publication.

Design and fabrication of a novel low cost hotplate micro gas sensor

Lactate Monitoring in Organotypic 3D Cell Cultures

CO2 Sensing in Medicine

In this paper, a foil-based BioMEMS for the electrochemical detection of troponin I, a marker for myocardial infarction is presented.

Gerald Urban

Papers

A novel multiparametric microphysiometry system for dynamic cell culture monitoring

Design and fabrication of a novel low cost hotplate micro gas sensor

Lactate Monitoring in Organotypic 3D Cell Cultures

CO2 Sensing in Medicine

BioMEMS for the electrochemical detection of troponin I