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.

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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

This paper shows a correlation between surface effective porosity due to various sintering regimes and humidity sensitive electrical properties of the perovskite-based bulk type humidity sensors. Furthermore, room temperature humidity transduction mechanism of the thick film type humidity sensors was studied in details through electrochemical impedance spectroscopy (EIS) and major transmissive components were detected by fitting to the equivalent circuits. The materials were synthesized employing solid state reaction and bulk and film type devices were fabricated by hydraulic pressing and screen printing techniques, respectively. The morphological and elemental characterizations were carried on using FESEM, EFTEM, and EDX. Physical properties including open porosity/bulk density were investigated through ASTM methods. An innovative self-designed material test fixture with ceramic supports was fabricated for high S/N ratio electrical measurement of the bulk samples. All the sensors were set up at 20-95% RH. The morphological, physical, and electrical results of bulk pellets indicate direct correlation of the open cavities and AC conduction. Presence of the ionic transport is clearly observed from the frequency-conductance spectra at room temperature. Noise-free detected behavior via EIS proves that proton transfer mechanism is a dominant responsible.

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Perovskites As Surface-Assisted Room Temperature Protonic Conductor Humidity Sensor

Real‐time monitoring of the cell/biomaterial interface for biomedical applications can significantly improve the assessment of biomaterials. However, currently there are no multiparametric real‐time monitoring systems for the ex vivo assessment of biomaterials. This study presents a method for monitoring of cell and tissue response to biomaterials based on microsensor read‐outs of pH, O2, and impedance. In vitro, the sensors are compatible with cells implants. For ex vivo measurements, either a biodegradable polymer poly(lactic‐co‐glycolic acid) or a protein‐repellent plasma polymer nanofilm is coated onto sensor arrays and placed on the chorioallantoic membrane of avian embryo ex ovo cultures. Signals related to dissolved oxygen, pH, and electrical impedance are continuously acquired for up to 90 h. Optical observation, immunohistochemical examination of CD45, and Haematoxylin and Eosin (H&E) staining show different unspecific immune responses. Tissue inflammation, capsule formation, and neovascularization are observed. These results correlate well with the type of coating material and the signal patterns acquired by the chemosensors. In addition, tissue death can be inferred from sensor signal patterns. This system is intended to enable continuous monitoring of biomaterials and is envisioned as a prescreening tool to provide real‐time monitoring of cell/biomaterial interface and also to reduce animal testing for biomaterial assessment purposes.

Multimodal Chemosensor‐Based, Real‐Time Biomaterial/Cell Interface Monitoring

Florinel-Gabriel Banica: Chemical sensors and biosensors: Fundamentals and applications

A Nitric oxide (NO) electrochemical sensor for hypoxic, tumor cell culture applications is developed. Qualitative analysis of the electrode has been studied by cyclic voltammetry. NO amperometric measurement methods have been extensively analyzed. Square wave voltammetry method is found to be one of the optimal methods for the measurement of NO in cell cultures. A hypoxic tumor cell culture measurement (MCF-7 cell type) has also been conducted to observe the NO response to hypoxia.

Optimising a Nitric oxide sensing technique for hypoxic tumor cell cultures

A full wafer fabrication process is presented for fabrication of microfluidic chips with integrated electroplated electrodes. The process is based on structured dry film resist on glass. The photoresist is bonded to a second glass substrate using heat and pressure. The chemical stability of the resist allows electroplating of electrodes after structuring the microfluidic network. At the same time it serves as an electroplating mask. The method gives full design flexibility to the user, is very fast and extremely simple. The process is used for creating electrophoretic chips with an integrated sacrificial silver-chloride electrode for bubble-free actuation.

Gerald Urban

Papers

Perovskites As Surface-Assisted Room Temperature Protonic Conductor Humidity Sensor

Multimodal Chemosensor‐Based, Real‐Time Biomaterial/Cell Interface Monitoring

Florinel-Gabriel Banica: Chemical sensors and biosensors: Fundamentals and applications

Optimising a Nitric oxide sensing technique for hypoxic tumor cell cultures

Full Wafer Fabrication Process for Microfluidic Glass Chips with Electroplated Electrodes