Continous, non-invasive monitoring of oxygen consumption in a parallelized microfluidic system provides novel insight into the response to nutrients and drugs of primary human hepatocytes.

Oxygen plays a fundamental role in cellular energy metabolism, differentiation and cell biology in general. Consequently, oxygen sensing can be used to assess cell vitality and detect specific mechanisms of toxicity. In 2D models currently used, the oxygen supply provided by diffusion is generally too low, especially for cells having a high oxygen demand.

Parallelizable Microfluidic Platform to Model and Assess In Vitro Cellular Barriers: Technology and Application to Study the Interaction of 3D Tumor Spheroids with Cellular Barriers.

Endothelial and epithelial cellular barriers play a vital role in the selective transport of solutes and other molecules. The properties and function of these barriers are often affected in case of inflammation and disease. Modelling cellular barriers in vitro can greatly facilitate studies of inflammation, disease mechanisms and progression, and in addition, can be exploited for drug screening and discovery.

HepaChip-MP - a twenty-four chamber microplate for a continuously perfused liver coculture model.

HepaChip microplate (HepaChip-MP) is a microfluidic platform comprised of 24 independent culture chambers with continuous, unidirectional perfusion. In the HepaChip-MP, an automated dielectrophoresis process selectively assembles viable cells into elongated micro tissues. Freshly isolated primary human hepatocytes (PHH) and primary human liver endothelial cells (HuLEC) were successfully assembled as cocultures aiming to mimic the liver sinusoid.

A novel microfluidic 3D platform for culturing pancreatic ductal adenocarcinoma cells: comparison with in vitro cultures and in vivo xenografts.

The integration of microfluidics and cell biology has reached a significant milestone with the development of "organ-on-chips", smart technological platforms that, once applied to the study of human diseases, such as cancer, might ultimately contribute to design personalised treatments and hence improve health outcomes. This paper reports that the combination of microfluidics and dielectrophoresis (DEP) allows to culture different pancreatic ductal adenocarcinoma (PDAC) human cell lines into a cyclic olefin polymer (COP) chamber (HepaChip), enriched by the extracellular matrix (ECM) protein collagen. We show that PDAC cells cultured into the HepaChip (1) are vital and grow, provided they properly attach to collagen; (2) show morphological appearance and growth characteristics closer to those of cells grown as spheroids than as classical 2 dimensional (2D) in vitro cultures.

Introduction to polymer-based solid-contact ion-selective electrodes-basic concepts, practical considerations, and current research topics.

This review aims at providing an introductory overview for researchers new to the field of ion-selective electrodes. Both state of the art technology and novel developments towards solid-contact reference (sc-RE) and solid-contact ion selective electrodes (sc-ISE) are discussed. This technology has potentially widespread and important applications provided certain performance criteria can be met.

Corrigendum: Can Nanofluidic Chemical Release Enable Fast, High Resolution Neurotransmitter-Based Neurostimulation?

[This corrects the article on p. 138 in vol. 10, PMID: 27065794.

Expanding an Efficient, Electrically Driven and CNT-Tagged P450 System into the Third Dimension: A Nanowired CNT-Containing and Enzyme-Stabilising 3 D Sol-Gel Electrode.

Although electrochemically catalysed P450 reactions have been described, their efficiency and applicability remained limited. This is mostly due to low enzyme activity, laborious protein immobilisation and the small electrode surface. We established a novel protein immobilisation method for a determined orientation and electrical wiring of the enzyme without post-expression modification.

Can Nanofluidic Chemical Release Enable Fast, High Resolution Neurotransmitter-Based Neurostimulation?

Artificial chemical stimulation could provide improvements over electrical neurostimulation. Physiological neurotransmission between neurons relies on the nanoscale release and propagation of specific chemical signals to spatially-localized receptors. Current knowledge of nanoscale fluid dynamics and nanofluidic technology allows us to envision artificial mechanisms to achieve fast, high resolution neurotransmitter release.

Cell-laden hydrogel/titanium microhybrids: Site-specific cell delivery to metallic implants for improved integration.

Unlabelled: Porous titanium implants are widely used in dental, orthopaedic and otorhinolaryngology fields to improve implant integration to host tissue. A possible step further to improve the integration with the host is the incorporation of autologous cells in porous titanium structures via cell-laden hydrogels. Fast gelling hydrogels have advantageous properties for in situ applications such as localisation of specific cells and growth factors at a target area without dispersion.

Electrochemical etching of micro-pores in medical grade cobalt-chromium alloy as reservoirs for drug eluting stents.

Drug eluting stents (DES) have shown efficacy in reducing restenosis after angioplasty followed by application of a coronary stent. However, polymer matrices typically used for immobilizing drugs on the stent surface may cause irritation and have limited drug loading capacity. In contrast, drug loading into micro- or nanopores created within the stent material could avoid these problems.

Microfluidic chip system for the selection and enrichment of cell binding aptamers.

Aptamers are promising cell targeting ligands for several applications such as for the diagnosis, therapy, and drug delivery. Especially, in the field of regenerative medicine, stem cell specific aptamers have an enormous potential. Using the combinatorial chemistry process SELEX (Systematic Evolution of Ligands by Exponential enrichment), aptamers are selected from a huge oligonucleotide library consisting of approximately 10(15) different oligonucleotides.

Moving the solid phase: a platform technology for cartridge based sandwich immunoassays.

We report on a cartridge based platform for complex immunoassay formats that allows for flexible adaption of individual steps. It is a sample-to-answer system which is quantitative as well as sensitive. The target molecules are detected through a magnetic bead-based fluorescence sandwich immunoassay.

PEDOT-CNT Composite Microelectrodes for Recording and Electrostimulation Applications: Fabrication, Morphology, and Electrical Properties.

Composites of carbon nanotubes and poly(3,4-ethylenedioxythiophene, PEDOT) and layers of PEDOT are deposited onto microelectrodes by electropolymerization of ethylenedioxythiophene in the presence of a suspension of carbon nanotubes and polystyrene sulfonate. Analysis by FIB and SEM demonstrates that CNT-PEDOT composites exhibit a porous morphology whereas PEDOT layers are more compact. Accordingly, capacitance and charge injection capacity of the composite material exceed those of pure PEDOT layers.

Numerical modelling and measurement of cell trajectories in 3-D under the influence of dielectrophoretic and hydrodynamic forces.

This research is part of a program aiming at the development of a fluidic microsystem for in vitro drug testing. For this purpose, primary cells need to be assembled to form cellular aggregates in such a way as to resemble the basic functional units of organs. By providing for in vivo-like cellular contacts, proper extracellular matrix interaction and medium perfusion it is expected that cells will retain their phenotype over prolonged periods of time.

"Artificial micro organs"--a microfluidic device for dielectrophoretic assembly of liver sinusoids.

In order to study possible toxic side effects of potential drug compounds in vitro a reliable test system is needed. Predicting liver toxicity presents a major challenge of particular importance as liver cells grown in a cell culture suffer from a rapid loss of their liver specific functions. Therefore we are developing a new microfluidic test system for liver toxicity.

Multiwalled carbon-nanotube-functionalized microelectrode arrays fabricated by microcontact printing: platform for studying chemical and electrical neuronal signaling.

A facile method is proposed for the deposition of multiwalled carbon nanotube (MWCNT) layers onto microelectrode arrays by means of a microcontact printing technique, leading to the fabrication of MEAs characterized by well defined electrical and morphological properties. Using polydimethyl siloxane stamps, produced from different mold designs, a flexibility of printing is achieved that provides access to microscale, nanostructured electrodes. The thickness of MWCNT layers can be exactly predetermined by evaluating the concentration of the MWCNT solution employed in the process.

Chemical stimulation of adherent cells by localized application of acetylcholine from a microfluidic system.

Chemical stimulation of cells is inherently cell type selective in contrast to electro-stimulation. The availability of a system for localized application of minute amounts of chemical stimulants could be useful for dose related response studies to test new compounds. It could also bring forward the development of a novel type of neuroprostheses.

A method for patterned in situ biofunctionalization in injection-molded microfluidic devices.

We developed a method to modify the surface in injection molded polymer microdevices prior to bonding and to pattern biomolecules in the completed microsystem in situ by a sequence of simple perfusion steps directly before utilization of the device. This method is compatible with production technology such as injection molding and bonding processes currently employed in the fabrication of polymer microsystems. It solves the problem of the inherent incompatibility of biomolecules with microfabrication technology as it allows for the biofunctionalization step to be performed after completion of the microsystem.

MicroPrep: chip-based dielectrophoretic purification of mitochondria.

We have developed a microfluidic system--microPrep--for subcellular fractionation of cell homogenates based on dielectrophoretic sorting. Separation of mitochondria isolated from a human lymphoblastoid cell line was monitored by fluorescence microscopy and further characterized by western blot analysis. Robust high throughput and continuous long-term operation for up to 60 h of the microPrep chip system with complex biological samples became feasible as a result of a comprehensive set of technical measures: (i) coating of the inner surfaces of the chip with BSA, (ii) application of mechanical actuators to induce periodic flow patterns, (iii) efficient cooling of the device to ensure integrity of organelle, (iv) a wide channel to provide for high fluidic throughput, and (v) integration of a serial arrangement of 10 dielectrophoretic deflector units to enable separation of samples with a high particle load without clogging.

Localized functional chemical stimulation of TE 671 cells cultured on nanoporous membrane by calcein and acetylcholine.

Acetylcholine sensitive TE 671 cells were cultured on nanoporous membranes and chemically stimulated by localized application of i), calcein-AM and ii), acetylcholine, respectively, onto the bottom face of the membrane employing an ink jet print head. Stimulus correlated response of cells was recorded by fluorescence microscopy with temporal and spatial resolution. Calcein fluorescence develops as a result of intracellular enzymatic conversion of calcein-AM, whereas Ca(2+) imaging using fluo-4 dye was employed to visualize cellular response to acetylcholine stimulation.

Accumulation and trapping of hepatitis A virus particles by electrohydrodynamic flow and dielectrophoresis.

Hepatitis A virus particles (d = 27 nm) were successfully accumulated and trapped in a microfluidic system by means of a combination of electrohydrodynamic flow and dielectrophoretic forces. Electric fields were generated in a field cage consisting of eight microelectrodes. In addition, high medium conductance (0.

Measuring single-bond rupture forces using high electric fields in microfluidic channels and DNA oligomers as force tags.

The disruption force of specific biotin-streptavidin bonds was determined using DNA oligomers as force tags. Forces were generated by an electric field acting on a biotinylated fluorescently labeled DNA oligomer. DNA oligomers were immobilized via biotin-streptavidin bonds on the walls of microfluidic channels.

Microdevices for manipulation and accumulation of micro- and nanoparticles by dielectrophoresis.

Microfluidic devices with three-dimensional (3-D) arrays of microelectrodes embedded in microchannels have been developed to study dielectrophoretic forces acting on synthetic micro- and nanoparticles. In particular, so-called deflector structures were used to separate particles according to their size and to enable accumulation of a fraction of interest into a small sample volume for further analysis. Particle velocity within the microchannels was measured by video microscopy and the hydrodynamic friction forces exerted on deflected particles were determined according to Stokes law.

Biostability of micro-photodiode arrays for subretinal implantation.

Micro-photodiode arrays based on semiconductor chip technology are being developed to replace degenerated photoreceptor cells in the retina. Electric current is generated in tiny micro-photodiodes and delivered to the adjacent tissue by micro-electrodes. One of the main requirements of a sub-retinal implantable device is long-term stability versus corrosion in vivo (biostability).