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.

/pdf/hydrogels-in-biology-and-medicine-from-molecular-principles-3lowrzjjsl.pdf

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

We present a cell culture monitoring platform to study effects of photodynamic therapy (PDT) on cancer cells. For the first time, it was possible to observe differences in cellular respiration at the transition between treated and untreated tumor cells in the same culture. Therewith more realistic in vitro studies of treatment efficiency and edge effects during PDT are possible. This resembles the spatially limited exposure in the in vivo situation. The sensor platform comprises an optically transparent microsensor chip with an integrated array of electrochemical oxygen microsensors and a LED light source for the photodynamic treatment.

Oxygen Microsensor Array to Study Spatial Efficacy of Photodynamic Therapy in Vitro

For the purpose of a direct methanol fuel cell (DMFC), this research investigates the kinetics of methanol oxidation in a porous layer consisting of external hierarchical nanostructures through 2D COMSOL simulation. Three different lengths of nanowires (L) were considered in simulations. The investigation showed that specific activity was reversely proportional to nanowires length and roughness factor (Rf). However, the current density increased by increasing Rf. Although the current density in case of L = 200 nm and 500 nm was identical with respect to Rf, there was a slight deviation when L = 1000 nm due to the changing from kinetic to diffusion controlled regime, which was identified by investigation of Thiele modulus. The catalytic efficiency for L = 1000 nm dropped to 50% at Rf = 140, whereas the high efficiency with no mass-transport limitation was achieved by shorter nanowires. Therefore, increasing Rf within the simulation range resulted in increasing the total catalytic activity but simultaneously decreasing the specific activity because of the decrease in pore accessibility and catalytic efficiency of nanostructures.

http://iopscience.iop.org/article/10.1088/1742-6596/660/1/012129/pdf

A novel study of the kinetics of external hierarchical nanostructures in methanol fuel cell

EINLEITUNG: In vielen Bereichen der Medizin, unter anderem in der Diabetologie und in der Intensivmedizin, wächst die Notwendigkeit, wichtige metabolische Parameter on-line messen zu können. Nur mit Monitoring und bettseitiger Analyse während Operationen und in der Intensivstation lassen sich Konzentrationsschwankungen und Trends frühzeitig erkennen, und geben damit dem Arzt die Möglichkeit bei Krisen bereits vor derem vollen Ausbruch zu intervenieren. Um diesen Anforderungen gerecht werden zu können, bedarf es zuverlässiger, einfach handhabbarer und genauer Sensoren, die vorteilhafterweise zu integrierten Multisensoren kombiniert sein sollen. Miniaturisierte Mikrosensoren für die Messung von Glukose, Laktat, Glutamat [2], pH [1], O2 [3], CO2, Strömung und Temperatur wurden für den Einsatz in biologischen Medien entwickelt. Zur Zeit werden die mikromechanischen Strömungssensoren für die Anwendungen Infusionskontrolle und Hydrocephalustherapie getestet [4]. Die mittels mikroelektronischer Technologien gefertigten Sensorarrays müssen, um ihren humanmedizinischen klinischen Einsatz zu ermöglichen, in Mikrosysteme implementiert werden. Sowohl SiliziumMikrobearbeitung als auch diverse Hybridtechnologien wurden modifiziert und zur Realisierung des „Labors am Chip\" verwendet.

https://www.degruyter.com/view/j/bmte.1996.41.issue-s1/bmte.1996.41.s1.272/bmte.1996.41.s1.272.pdf

Sensor-Mikrosysteme für klinische Monitoring-Anwendungen

New imidazole derivatives with fungistatic activity were synthesized at the NCRSRVI branch of FSBSC Federal Rostov Agrarian Scientific Center. The initial compound 4,5-dichlorimidazole was obtained according to the method described in the literature [3]. Structures 1, 4, 6, 7, 8 - 11, 14 - 17, 19, 20, 22, 24 they were synthesized by alkylation of 4,5-dichlorimidazole with corresponding halide alkyls in an alkaline medium. Alcohol 5 was obtained by reducing ketone with sodium borohydride in ethanol. Bigeterocycles 10, 13 were obtained by the reaction of 4,5-dichlorimidazole with corresponding chloronitropyridines by boiling in dimethylformamide in the presence of potassium carbonate. Compound 10 was obtained under similar conditions, but ortho-chloronitrobenzene was used as an aryl derivative. The preparation 23 was obtained by acylation using a chlorocarbon ester of the corresponding N-(4-aminophenylmethyl) 4,5-dichlorimidazole, which, in turn, was synthesized from a nitro derivative by reduction with iron in ethanol in the presence of a catalytic amount of hydrochloric acid. Preparation 18 is obtained from the methyl ester of 4,5-dichlorimidazole and acetic acid and hydrazine in an alcoholic medium. The study of fungistatic activity showed that the size of the culture growth retardation zone crucially depends on the type of substituents in the nitrogen atom of the imidazole cycle. First of all, this applies to the lipophilicity of the substituent: the higher the lipophilicity (of the compound 1, 4, 6, 7, 20, 22-24), the higher the activity of the connection. However, lipophilicity obviously should not exceed certain limits: the most lipophilic compounds 2 and 3 are significantly inferior in activity to slightly less lipophilic compounds 1, 4, 6, 7, 20, 22-24. Polar substituents of the nitrogen atom (compounds 5, 8, 11, 16-18, 23) completely suppress fungistatic activity. The aryl substituent of the nitrogen atom of the imidazole ring (compound 10), as well as the nitrogetaryl substituents (compounds 12 and 13) have significant fungistatic activity.

Search for fungistatics in the imidazole series

In this work we performed experiments to compare the efficacy of disinfectants and plasma on biofilms of the bacterial strains E. coli K12 and E. faecalis Symbioflor® grown for 20 h. The disinfecting agents aqueous ethanol (70 %), peracetic acid (PAA) (15 %) and sodium hypochlorite (NaOCl) (3 %) were used and compared to an atmospheric plasma jet. Sterile Mueller-Hinton-1 (MH1) growth medium and deionized (DI) water were used as negative controls to replace the bacterial suspension and/or the disinfectant agent. For these investigations a thermal biofilm sensor was used to detect not only the effectiveness of chemical substances or the plasma jet in removing biofilm, but also possible growth after the treatment. In these experiments the biofilm was grown for 20 h and the different disinfection methods were then applied. The plasma jet and the NaOCl were the most effective treatments whereby the plasma jets effect can be instantly switched on and off while NaOCl is a liquid solution which exerts its effect as long as it remains in place. 

Gerald Urban

Papers

Oxygen Microsensor Array to Study Spatial Efficacy of Photodynamic Therapy in Vitro

A novel study of the kinetics of external hierarchical nanostructures in methanol fuel cell

Sensor-Mikrosysteme für klinische Monitoring-Anwendungen

Search for fungistatics in the imidazole series

Analysis of the effects of disinfectants and plasma treatment on biofilm growth by a thermal flow sensor for real time measurements