Towards micro electrical impedance tomography on chip

This work presents initial design and testing of a miniaturized electrical impedance tomography platform. Electrical impedance tomography (EIT) provides a low-cost, non-invasive, radiation-free type of imaging and can be relatively easily implemented on other miniaturized systems like microfluidics. Herein, we describe a miniaturized EIT on chip, along with its measurement setup and image reconstruction pipeline. First imaging results demonstrating a well-functioning setup are presented and form the basis for further investigations

Biphasic biocatalytic testosterone dehydrogenation in microfluidic droplets

Two-phase biocatalysis is commonly used for the bioconversion of water-insoluble chemical and pharmaceutical compounds. In research laboratories, such processes often take place in flasks and are driven and limited by slow diffusive processes. In this work, we developed droplet-based microfluidic systems and used them to perform testosterone dehydrogenation. The use of microdroplets as reaction vessels offers the advantage of greatly improved diffusion rates due to significantly increased surface-to-volume ratio. We found that indeed reaction time was reduced from tens of minutes to tens of seconds without sacrificing conversion efficiency. This demonstrates the potential of droplet-based two-phase biocatalysis

Microsystems for Cell Cultures

Microfabricated systems are increasingly being utilized in biotechnological, biomedical, and pharmaceutical research and development as replacements for traditional in vitro cell cultures, bioreactors, and animal experiments (Figure 1) [...

Integrated Microfluidics for Single‐Cell Separation and On‐Chip Analysis: Novel Applications and Recent Advances

From deciphering infection and disease mechanisms to identifying novel biomarkers and personalizing treatments, the characteristics of individual cells can provide significant insights into a variety of biological processes and facilitate decision-making in biomedical environments. Conventional single-cell analysis methods are limited in terms of cost, contamination risks, sample volumes, analysis times, throughput, sensitivity, and selectivity. Although microfluidic approaches have been suggested as a low-cost, information-rich, and high-throughput alternative to conventional single-cell isolation and analysis methods, limitations such as necessary off-chip sample pre- and post-processing as well as systems designed for individual workflows have restricted their applications. In this review, a comprehensive overview of recent advances in integrated microfluidics for single-cell isolation and on-chip analysis in three prominent application domains are provided: investigation of somatic cells (particularly cancer and immune cells), stem cells, and microorganisms. Also, the use of conventional cell separation methods (e.g., dielectrophoresis) in unconventional or novel ways, which can advance the integration of multiple workflows in microfluidic systems, is discussed. Finally, a critical discussion related to current limitations of integrated microfluidic single-cell workflows and how they could be overcome is provided

Two-Phase Biocatalysis in Microfluidic Droplets

This Perspective discusses the literature related to two-phase biocatalysis in microfluidic droplets. Enzymes used as catalysts in biocatalysis are generally less stable in organic media than in their native aqueous environments; however, chemical and pharmaceutical compounds are often insoluble in water. The use of aqueous/organic two-phase media provides a solution to this problem and has therefore become standard practice for multiple biotransformations. In batch, two-phase biocatalysis is limited by mass transport, a limitation that can be overcome with the use of microfluidic systems. Although, two-phase biocatalysis in laminar flow systems has been extensively studied, microfluidic droplets have been primarily used for enzyme screening. In this Perspective, we summarize the limited published work on two-phase biocatalysis in microfluidic droplets and discuss the limitations, challenges, and future perspectives of this technology

Self-Learning Microfluidic Platform for Single-Cell Imaging and Classification in Flow

Single-cell analysis commonly requires the confinement of cell suspensions in an analysis chamber or the precise positioning of single cells in small channels. Hydrodynamic flow focusing has been broadly utilized to achieve stream confinement in microchannels for such applications. As imaging flow cytometry gains popularity, the need for imaging-compatible microfluidic devices that allow for precise confinement of single cells in small volumes becomes increasingly important. At the same time, high-throughput single-cell imaging of cell populations produces vast amounts of complex data, which gives rise to the need for versatile algorithms for image analysis. In this work, we present a microfluidics-based platform for single-cell imaging in-flow and subsequent image analysis using variational autoencoders for unsupervised characterization of cellular mixtures. We use simple and robust Y-shaped microfluidic devices and demonstrate precise 3D particle confinement towards the microscope slide for high-resolution imaging. To demonstrate applicability, we use these devices to confine heterogeneous mixtures of yeast species, brightfield-image them in-flow and demonstrate fully unsupervised, as well as few-shot classification of single-cell images with 88% accuracy

Space-Filling Curve Resistor on Ultra-Thin Polyetherimide Foil for Strain Impervious Temperature Sensing

Monitoring process parameters in the manufacture of composite structures is key to ensuring product quality and safety. Ideally, this can be done by sensors that are embedded during production and can remain as devices to monitor structural health. Extremely thin foil-based sensors weaken the finished workpiece very little. Under ideal conditions, the foil substrate bonds with the resin in the autoclaving process, as is the case when polyetherimide is used. Here, we present a temperature sensor as part of an 8 µm thick multi-sensor node foil for monitoring processing conditions during the production and structural health during the lifetime of a construction. A metallic thin film conductor was shaped in the form of a space-filling curve to suppress the influences of resistance changes due to strain, which could otherwise interfere with the measurement of the temperature. FEM simulations as well as experiments confirm that this type of sensor is completely insensitive to the direction of strain and sufficiently insensitive to the amount of strain, so that mechanical strains that can occur in the composite curing process practically do not interfere with the temperature measurement. The temperature sensor is combined with a capacitive sensor for curing monitoring based on impedance measurement and a half-bridge strain gauge sensor element. All three types are made of the same materials and are manufactured together in one process flow. This is the key to cost-effective distributed sensor arrays that can be embedded during production and remain in the workpiece, thus ensuring not only the quality of the initial product but also the operational reliability during the service life of light-weight composite constructions

3D Focusing in Simple Microfluidic Devices for Continuous-flow Single-cell Imaging [data set]

Accompanying data for the manuscript "3D Focusing in Simple Microfluidic Devices for Continuous-flow Single-cell Imaging"

Batch-to-batch variation of polymeric photovoltaic materials: Its origin and impacts on charge carrier transport and device performances

A detailed investigation of the impact of molecular weight distribution of a photoactive polymer, poly[N-9\u2032-heptadecanyl-2,7-carbazole-alt-5,5-(4\u2032,7\u2032-di-2-thienyl-2\u2032,1\u2032,3\u2032-benzothiadiazole)] (PCDTBT), on photovoltaic device performance and carrier transport properties is reported. It is found that different batches of as-received polymers have substantial differences in their molecular weight distribution. As revealed by gel permeation chromatography (GPC), two peaks can generally be observed. One of the peaks corresponds to a high molecular weight component and the other peak corresponds to a low molecular weight component. Photovoltaic devices fabricated with a higher proportion of low molecular weight component have power conversion efficiencies (PCEs) reduced from 5.7% to 2.5%. The corresponding charge carrier mobility at the short-circuit region is also significantly reduced from 2.7 7 10-5 to 1.6 7 10-8 cm2 V-1 s-1. The carrier transport properties of the polymers at various temperatures are further analyzed by the Gaussian disorder model (GDM). All polymers have similar energetic disorders. However, they appear to have significant differences in carrier hopping distances. This result provides insight into the origin of the molecular weight effect on carrier transport in polymeric semiconducting materials. Batch-to-batch variation of the photovoltaic performance of devices based on commercial samples of the polymer poly[N-9\u2032-heptadecanyl-2,7-carbazole-alt-5,5- (4\u2032,7\u2032-di-2-thienyl-2\u2032,1\u2032,3\u2032-benzothiadiazole)] (PCDTBT) is reported, with efficiency ranging from 5.7% to 2.5%. As revealed by gel permeation chromatography, bimodal distributions are observed in the molecular weight. Charge transport data suggest that low molecular weight components increase the average hopping distance, resulting in lower mobility and poorer photovoltaic performance. \ua9 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Peer reviewed: YesNRC publication: Ye

Self-loading microfluidic platform with ultra-thin nanoporous membrane for organ-on-chip by wafer-level processing

Embedded porous membranes are a key element of various organ-on-chip systems. The widely used commercial polymer membranes impose limits with regard to chip integration and thinness. We report a microfluidic chip platform with the key element of a monolithically integrated, ultra-thin (700 nm) nanoporous membrane made of ultra-low-stress (<35 MPa) SixNy for culturing and testing reconstructed tissue. The membrane is designed to support various in vitro tissues including co-cultures and to allow passage of molecules but not of cells. A digital laser write method was used to produce nanopores with deterministic but highly flexible positioning within the membrane. A thin layer of photoresist was exposed by accumulation of femtosecond pulses for local two-photon polymerization, which allowed nanopores as small as 350 nm in diameter to be generated through the membranes in a subsequent plasma etch process. The fabricated membranes were used to separate a microfluidic chip into two compartments, which are connected to the outside by microchannel structures. With unique side inlets for fluids, all cells are exposed to identical flow velocities and shear stresses. With the hydrophilic nature of chip materials the self-loading seeding is controlled bottom-up by capillary forces, which makes the seeding procedure homogeneous and less dependent on the operator. The chip is designed to allow fabrication by wafer-level MEMS manufacturing technologies without critical assembly steps, thereby promoting reproducibility and scale-up of fabrication. In order to establish a fully functional test system to be used in a lab incubator, a holder for the bare chip was designed and 3D-printed with additional elements for gravity driven pumping. In order to mimic physiological conditions, the holder was designed to provide not only media delivery but also appropriate shear stress to the tissue. To prove usability, murine microvascular endothelial cells (muMEC) were seeded on the membrane within the chip. Cell compatibility was confirmed after 3 days of dynamic cultivation using fluorescence live/dead assays. Cultivation proved to be reproducible and led to confluent layers with cells preferentially grown on nanoporous areas. The system can in future be cost effectively manufactured in larger quantities in MEMS foundries and can be used for a wide variety of in vitro tissues and test scenarios including pumpless operation within cell incubator cabinets