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Showing papers in "Microsystems & Nanoengineering in 2015"


Journal ArticleDOI
TL;DR: This work establishes an innovative approach to construct arbitrary 3D systems with embedded electrical structures as integrated circuitry for various applications, including the demonstrated passive wireless sensors.
Abstract: Three-dimensional (3D) additive manufacturing techniques have been utilized to make 3D electrical components, such as resistors, capacitors, and inductors, as well as circuits and passive wireless sensors. Using the fused deposition modeling technology and a multiple-nozzle system with a printing resolution of 30 μm, 3D structures with both supporting and sacrificial structures are constructed. After removing the sacrificial materials, suspensions with silver particles are injected subsequently solidified to form metallic elements/interconnects. The prototype results show good characteristics of fabricated 3D microelectronics components, including an inductor–capacitor-resonant tank circuitry with a resonance frequency at 0.53 GHz. A 3D “smart cap” with an embedded inductor–capacitor tank as the wireless passive sensor was demonstrated to monitor the quality of liquid food (e.g., milk and juice) wirelessly. The result shows a 4.3% resonance frequency shift from milk stored in the room temperature environment for 36 h. This work establishes an innovative approach to construct arbitrary 3D systems with embedded electrical structures as integrated circuitry for various applications, including the demonstrated passive wireless sensors. A three-dimensional (3D) printing technology makes possible arbitrary-shaped, integrated microelectronic components and circuitry with existing products such as food containers. Customizing microsystems through layer-by-layer manufacturing techniques is an attractive proposition. However, the polymers used typically offer poor conductivity, making them unsuitable for microelectronic device applications. Liwei Lin and colleagues from the USA and Hsinchu address this problem by printing resistor, capacitor, and inductor devices composed of hollow polymer tubes. By injecting silver paste into the tubes, curing the metal, and removing the polymer support, they are able to generate intricate yet functional 3D circuits. The team demonstrates the potential of their approach by creating a “smart cap”—a wireless inductive sensor incorporated into a milk carton lid. The sensor detects shifts in liquid dielectric constant signals to warn consumers about potential food safety issues.

250 citations


Journal ArticleDOI
TL;DR: Traditional as well as innovative and emerging approaches to MEMS and IC integration are reviewed, including approaches based on the hybrid integration of multiple chips (multi- chip solutions) as wellAs system-on-chip solutions based on wafer-level monolithic integration and heterogeneous integration techniques.
Abstract: The majority of microelectromechanical system (MEMS) devices must be combined with integrated circuits (ICs) for operation in larger electronic systems. While MEMS transducers sense or control phys ...

216 citations


Journal ArticleDOI
TL;DR: Li et al. as discussed by the authors presented an electrochemical microfluidic paper-based analytical device (EμPAD) for glucose detection, featuring a highly sensitive working electrode (WE) decorated with zinc oxide nanowires (ZnO NWs).
Abstract: This paper reports an electrochemical microfluidic paper-based analytical device (EμPAD) for glucose detection, featuring a highly sensitive working electrode (WE) decorated with zinc oxide nanowires (ZnO NWs). In addition to the common features of μPADs, such as their low costs, high portability/disposability, and ease of operation, the reported EμPAD has three further advantages. (i) It provides higher sensitivity and a lower limit of detection (LOD) than previously reported μPADs because of the high surface-to-volume ratio and high enzyme-capturing efficiency of the ZnO NWs. (ii) It does not need any light-sensitive electron mediator (as is usually required in enzymatic glucose sensing), which leads to enhanced biosensing stability. (iii) The ZnO NWs are directly synthesized on the paper substrate via low-temperature hydrothermal growth, representing a simple, low-cost, consistent, and mass-producible process. To achieve superior analytical performance, the on-chip stored enzyme (glucose oxidase) dose and the assay incubation time are tuned. More importantly, the critical design parameters of the EμPAD, including the WE area and the ZnO-NW growth level, are adjusted to yield tunable ranges for the assay sensitivity and LOD. The highest sensitivity that we have achieved is 8.24 μA·mM−1·cm−2, with a corresponding LOD of 59.5 μM. By choosing the right combination of design parameters, we constructed EμPADs that cover the range of clinically relevant glucose concentrations (0−15 mM) and fully calibrated these devices using spiked phosphate-buffered saline and human serum. We believe that the reported approach for integrating ZnO NWs on EμPADs could be well utilized in many other designs of EμPADs and provides a facile and inexpensive paradigm for further enhancing the device performance. A paper-based microfluidic biosensor with an electrode decorated with zinc oxide nanowires is used for sensitive detection of glucose. Microfluidic paper-based analytical devices (μPADs) are attractive platforms for diagnostic biosensing, particularly in areas lacking sophisticated medical resources, because they are inexpensive and easy to operate. Now, Xiao Li, Chen Zhao and Xinyu Liu at McGill University in Canada have produced a high-sensitivity electrochemical μPAD that incorporates a working electrode decorated with zinc oxide nanowires. The μPAD has enhanced biosensing performance and stability, and can be produced by a simple, low cost process. By judicial selection of the design parameters, the researchers produced μPADs that can accurately detect glucose in a clinically relevant concentration range (0—15 millimolar) in human serum. They consider that the performance of other electrochemical μPADs could be enhanced through the integration of zinc oxide nanowires.

134 citations


Journal ArticleDOI
TL;DR: In this paper, a micro-scale battery that harnesses energy from metallic corrosion to power implants while simultaneously dissolving was presented, which exhibited an energy density of 694 Wh kg−1 and a total volume of 0.02 cm3.
Abstract: This study presents the design, fabrication, and testing of biodegradable magnesium/iron batteries featuring polycaprolactone (PCL) as a packaging and functional material. The use of PCL encapsulation minimized the electrochemical cell volume and supported longer discharge lifetimes and higher discharge rates than state-of-the-art biodegradable batteries. Specifically, the electrodes were separated and insulated by a 5 µm-thick PCL layer that served as both a battery packaging material and a permeable coating for physiological solution to penetrate and activate the battery. A systematic investigation of the electrode size, discharge rates, electrolyte selection, and polymeric coating revealed the critical reactions and phenomena governing the performance of the Mg-based biodegradable batteries. Comparison with previous reports on biodegradable batteries and medical-grade non-degradable lithium-ion batteries demonstrated the superior performance of PCL-coated Mg/Fe batteries at these size scales, which exhibited an energy density of 694 Wh kg−1 and a total volume of 0.02 cm3. A battery that generates power by ‘eating’ itself in saline fluid could help extend the capabilities of biodegradable medical implants. Treating non-chronic ailments such as brain trauma or bone injuries with smart implants would allow physicians to remotely monitor the recovery process, but requires surgical removal of the device after healing. Transient implants that dissolve after a short exposure to physiological conditions offer a promising nonsurgical option but are currently limited to passive, low-power designs. Mark Allen from the University of Pennsylvania and his research group have fabricated a microscale battery that harnesses energy from metallic corrosion to power implants while simultaneously dissolving. Composed of magnesium and iron electrodes encapsulated by a biodegradable polycaprolactone salt-permeable mebrane, the team's micrometer-scale battery has a two order of magnitude higher energy density than comparable devices.

76 citations


Journal ArticleDOI
Jun Liu1, Jun Wen1, Zhuoran Zhang1, Haijiao Liu1, Yu Sun1 
TL;DR: Improvements in the spatial and temporal resolution of these measurements will provide fresh insight into how the intracellular environment affects the health of cells, the researchers conclude.
Abstract: Properties of organelles and intracellular structures play important roles in regulating cellular functions, such as gene expression, cell motility and metabolism. The ability to directly interrogate intracellular structures inside a single cell for measurement and manipulation has significant implications in the understanding of subcellular and suborganelle activities, diagnosing diseases, and potentially developing new therapeutic approaches. In the past few decades, a number of technologies have been developed to study single-cell properties. However, methods of measuring intracellular properties and manipulating subcellular structures have been largely underexplored. Due to the even smaller size of intracellular targets and lower signal-to-noise ratio than that in whole-cell studies, the development of tools for intracellular measurement and manipulation is challenging. This paper reviews emerging microsystems and nanoengineered technologies for sensing and quantitative measurement of intracellular properties and for manipulating structures inside a single cell. Recent progress and limitations of these new technologies as well as new discoveries and prospects are discussed. Measuring and manipulating biological processes in the tiny compartments inside a cell is crucial for understanding their function. Much can go wrong if the localization of intracellular events is disturbed: for example, cardiac arrhythmia can arise when electrical currents spread incorrectly among cells in the heart. Yu Sun and colleagues at the University of Toronto, Canada, review emerging methods for conducting precise measurements and manipulation inside cells. They describe tools that comprise a sensor attached to a device outside the cell, such as nanowires for recording electrical activity. They also discuss unattached probes that are delivered into the cell, such as nanoparticles for temperature and pH sensing. The researchers conclude that improvements in the spatial and temporal resolution of these measurements will provide fresh insight into how the intracellular environment affects the health of cells.

70 citations


Journal ArticleDOI
TL;DR: In this article, a microchip with three micropillars arranged in a triangular configuration and an xyz piezoelectric actuator was used to apply the circular vibration.
Abstract: We propose a novel on-chip 3D cell rotation method based on a vibration-induced flow. When circular vibration is applied to a microchip with micropillar patterns, a highly localized whirling flow is induced around the micropillars. The direction and velocity of this flow can be controlled by changing the direction and amplitude of the applied vibration. Furthermore, this flow can be induced on an open chip structure. In this study, we adopted a microchip with three micropillars arranged in a triangular configuration and an xyz piezoelectric actuator to apply the circular vibration. At the centre of the micropillars, the interference of the vibration-induced flows originating from the individual micropillars induces rotational flow. Consequently, a biological cell placed at this centre rotates under the influence of the flow. Under three-plane circular vibrations in the xy, xz or yz plane, the cell can rotate in both the focal and vertical planes of the microscope. Applying this 3D cell rotation method, we measured the rotational speeds of mouse oocytes in the focal and vertical planes as 63.7 ± 4.0° s−1 and 3.5 ± 2.1° s−1, respectively. Furthermore, we demonstrated the transportation and rotation of the mouse oocytes and re-positioned their nuclei into a position observable by microscope. Three-dimensional cell observation and manipulation, required during cellular surgery, rely on proper orientation of the target cell. Conventional cell rotation techniques using microscopic hand-like devices demand sophisticated equipment and highly skilled operators. Additionally, existing on-chip approaches exploiting electric, magnetic and optical forces involve intricate structures that are complex to fabricate. To simplify these systems, Takeshi Hayakawa and co-workers from Nagoya University, Japan, have developed a microfluidic chip that controls cell rotation through vibration. The chip consists of a glass surface decorated with three small pillars in a triangular arrangement. To achieve stable motion, the researchers apply in-plane and vertical circular vibrations, creating local vortexes around the pillars that cause a cell placed at their centre to rotate. This simple, high-performance method is expected to play a central role in future biotechnology research.

67 citations


Journal ArticleDOI
TL;DR: Agah et al. as discussed by the authors used microfabrication technology to demonstrate the single chip integration of the key components of a µGC system in a two-step planar fabrication process.
Abstract: Miniaturized gas chromatography (µGC) systems hold potential for the rapid analysis of volatile organic compounds (VOCs) in an extremely compact and low-power enabled platform. Here, we utilize microfabrication technology to demonstrate the single chip integration of the key components of a µGC system in a two-step planar fabrication process. The 1.5 × 3 cm microfluidic platform includes a sample injection unit, a micromachined semi-packed separation column (µSC) and a micro-helium discharge photoionization detector (µDPID). The sample injection unit consists of a T-shaped channel operated with an equally simple setup involving a single three-way fluidic valve, a micropump for sample loading and a carrier gas supply for subsequent analysis of the VOCs. The innovative sample injection technique described herein requires a loading time of only a few seconds and produces sharp and repeatable sample pulses (full width at half maximum of approximately 200 ms) at a carrier gas flow rate that is compatible with efficient chromatographic separation. Furthermore, our comprehensive characterization of the chip reveals that a wide variety of VOCs with boiling points in the range of 110–216 °C can be analyzed in less than 1 min by optimizing the flow and temperature programming conditions. Moreover, the analysis of four VOCs at the concentration level of one part per million in an aqueous sample (which corresponds to a headspace concentration in the lower parts-per-billion regime) was performed with a sampling time of only 6 s. The µDPID has demonstrated a linear dynamic range over three orders of magnitude. The system presented here could potentially be used to monitor hazardous VOCs in real time in industrial workplaces and residential settings. A chip-sized gas chromatograph can detect hazardous volatile organic compounds in seconds. To avoid thermal crosstalk, the three main components of a microscale gas chromatograph—injector, separation column and mass detector—are normally placed on separate chips. Dr. Masoud Agah and co-workers from Virginia Polytechnic Institute and State University, United States, have combined these components onto a single chip using an innovative setup. The team fabricated a microfluidic injector and alumina-based column in close proximity to reduce analysis time. As samples elute from the column, they are photoionized by a helium-based detector that spots picograms of organic molecules without relying on thermal pre-concentration. The integrated device detects contaminants such as chlorobenzene and xylene with an extremely sharp chromatographic peak—indicating that thermal effects are minimized—and at speeds that allow real-time monitoring of liquids and air.

61 citations


Journal ArticleDOI
TL;DR: Extracellular matrix (ECM)-based implantable neural electrodes (NEs) were achieved using a microfabrication strategy on natural-substrate-based organic materials to minimize the introduction of non-natural products into the brain.
Abstract: Extracellular matrix (ECM)-based implantable neural electrodes (NEs) were achieved using a microfabrication strategy on natural-substrate-based organic materials. The ECM-based design minimized the introduction of non-natural products into the brain. Further, it rendered the implants sufficiently rigid for penetration into the target brain region and allowed them subsequently to soften to match the elastic modulus of brain tissue upon exposure to physiological conditions, thereby reducing inflammatory strain fields in the tissue. Preliminary studies suggested that ECM-NEs produce a reduced inflammatory response compared with inorganic rigid and flexible approaches. In vivo intracortical recordings from the rat motor cortex illustrate one mode of use for these ECM-NEs.

51 citations


Journal ArticleDOI
TL;DR: Hesketh and Mahdavifar as mentioned in this paper developed a new measurement method and hardware configuration based on the processing of the transient response of a low thermal mass TCD to an electric current step.
Abstract: Micro-thermal conductivity detector (µTCD) gas sensors work by detecting changes in the thermal conductivity of the surrounding medium and are used as detectors in many applications such as gas chromatography systems. Conventional TCDs use steady-state resistance (i.e., temperature) measurements of a micro-heater. In this work, we developed a new measurement method and hardware configuration based on the processing of the transient response of a low thermal mass TCD to an electric current step. The method was implemented for a 100-µm-long and 1-µm-thick micro-fabricated bridge that consisted of doped polysilicon conductive film passivated with a 200-nm silicon nitride layer. Transient resistance variations of the µTCD in response to a square current pulse were studied in multiple mixtures of dilute gases in nitrogen. Simulations and experimental results are presented and compared for the time resolved and steady-state regime of the sensor response. Thermal analysis and simulation show that the sensor response is exponential in the transient state, that the time constant of this exponential variation was a linear function of the thermal conductivity of the gas ambient, and that the sensor was able to quantify the mixture composition. The level of detection in nitrogen was estimated to be from 25 ppm for helium to 178 ppm for carbon dioxide. With this novel approach, the sensor requires approximately 3.6 nJ for a single measurement and needs only 300 µs of sampling time. This is less than the energy and time required for steady-state DC measurements. Researchers in the USA have developed a fast, energy-efficient measurement technique for use in micrometer-sized thermal gas sensors. Small and fast sensors are crucial for gas chromatography and other applications. Thermal gas sensors operate by measuring the characteristic thermal conductivity of gasses and gas mixtures. Peter Hesketh and Alireza Mahdavifar from the Georgia Institute of Technology and co-workers heated a 100-micrometers-long silicon bridge on a chip using pulsed electrical currents then measured the electrical resistance of the element as it changed with temperature. The time-dependent changes of the electrical resistance were characteristic of the thermal conductivity of the surrounding gas, providing a gas-specific detection mechanism that takes less than 300 μs and uses only 3.6 nJ per measurement. These robust sensors are particularly attractive because their use of electrical pulses means that they consume far less energy than DC-based techniques.

42 citations


Journal ArticleDOI
TL;DR: A silicon-based probe that simultaneously measures L-glutamate levels and electrical activity at various locations in the brain with high spatial and temporal resolution is developed and expects it to provide insight into physiological and pathological pathways in live brain tissue, paving the way to new diagnostic and therapeutic approaches.
Abstract: L-glutamate, the most common excitatory neurotransmitter in the mammalian central nervous system (CNS), is associated with a wide range of neurological diseases. Because neurons in CNS communicate with each other both electrically and chemically, dual-mode (electric and chemical) analytical techniques with high spatiotemporal resolution are required to better understand glutamate function in vivo. In the present study, a silicon-based implantable microelectrode array (MEA) composed of both platinum electrochemical and electrophysiological microelectrodes was fabricated using micro-electromechanical system. In the MEA probe, the electrophysiological electrodes have a low impedance of 0.018 MΩ at 1 kHz, and the electrochemical electrodes show a sensitivity of 56 pA µM−1 to glutamate and have a detection limit of 0.5 µM. The MEA probe was used to monitor extracellular glutamate levels, spikes and local field potentials (LFPs) in the striatum of anaesthetised rats. To explore the potential of the MEA probe, the rats were administered to KCl via intraperitoneal injection. K+ significantly increases extracellular glutamate levels, LFP low-beta range (12–18 Hz) power and spike firing rates with a similar temporal profile, indicating that the MEA probe is capable of detecting dual-mode neuronal signals. It was concluded that the MEA probe can help reveal mechanisms of neural physiology and pathology in vivo. Abnormal transmission of L-glutamate can cause neurological disorders such as Parkinson's disease, stroke and epilepsy. In their search for effective treatments, researchers are deploying extensive efforts to understand this key neurotransmitter, which regulates receptors located at chemical synapses. However, their attempts often fail to analyze the syntrophic complexity of biochemical and electrical events occurring in neurons. Now, Xinxia Cai and co-workers from the Institute of Electronics, Chinese Academy of Sciences, Beijing, China, have developed a silicon-based probe that simultaneously measures L-glutamate levels and electrical activity at various locations in the brain with high spatial and temporal resolution. The implantable array combines electrochemical and electrophysiological microelectrodes created through MEMS and nanotechnology. The team expects it to provide insight into physiological and pathological pathways in live brain tissue, paving the way to new diagnostic and therapeutic approaches.

42 citations


PatentDOI
TL;DR: In this article, a variety of different electrophoretic separation methods and systems for sub-cellular Western blotting of single cells are described, and a detailed discussion of the use of these methods and their applications can be found.
Abstract: Electrophoretic separation methods and systems for performing the same are provided. The methods and systems find use in a variety of different electrophoretic separation applications, such as sub-cellular Western blotting of single cells.

Journal ArticleDOI
TL;DR: Holmes and Bohringer as mentioned in this paper reviewed the different physical mechanisms responsible for driving droplets across surfaces with active devices or micropatterned paths, including surface tension, where the force between liquid and substrate changes along the length of the surface, and contact line processes in which vertical oscillations of an asymmetrically patterned surface move the drops.
Abstract: This review article examines digital microfluidic systems that manipulate droplets through surface anisotropy. These systems are categorized as surface tension driven or contact line driven. Surface tension driven systems include electrowetting on dielectric, Marangoni flow on microheater arrays, and chemical gradient surfaces, whereas contact line driven systems include anisotropic ratchet conveyors, nanostructured Parylene ratchets, and tilted pillar arrays. This article describes the operating principles and outlines the fabrication procedures for each system. We also present new equations that unify several previous models of contact line driven systems. The strengths and weaknesses of each system are compared, with a focus on their ability to perform the generation, switching, fusion, and fission of droplets. Finally, we discuss current and potential future applications of these systems. Controlling the movement of liquid drops over millimeter distances enables on-chip chemical analysis for use in cheap and portable sensors. Key functions of digital microfluidic systems are creating droplets from a reservoir, combining and splitting them, and switching them between different paths. Hal Holmes and Karl Bohringer from the University of Washington review the different physical mechanisms responsible for driving droplets across surfaces with active devices or micropatterned paths. These transport mechanisms include surface tension, where the force between liquid and substrate changes along the length of the surface, and so-called contact line processes in which vertical oscillations of an asymmetrically patterned surface move the drops. Although both methods can create and merge droplets, there remains a need to develop contact line systems that can switch and split them.

Journal ArticleDOI
TL;DR: In this article, a massively parallel electron beam direct write (MPEBDW) system was proposed for high-speed massively parallel NN-EB lithography using an active-matrix-driving complementary metal-oxide semiconductor (CMOS) large-scale integration (LSI) system.
Abstract: Nanoscale lithographic technologies have been intensively studied for the development of the next generation of semiconductor manufacturing practices. While mask-less/direct-write electron beam (EB) lithography methods serve as a candidate for the upcoming 10-nm node approaches and beyond, it remains difficult to achieve an appropriate level of throughput. Several innovative features of the multiple EB system that involve the use of a thermionic source have been proposed. However, a blanking array mechanism is required for the individual control of multiple beamlets whereby each beamlet is deflected onto a blanking object or passed through an array. This paper reviews the recent developments of our application studies on the development of a high-speed massively parallel electron beam direct write (MPEBDW) lithography. The emitter array used in our study includes nanocrystalline-Si (nc-Si) ballistic electron emitters. Electrons are drifted via multiple tunnelling cascade transport and are emitted as hot electrons. The transport mechanism allows one to quickly turn electron beamlets on or off. The emitter array is a micro-electro-mechanical system (MEMS) that is hetero-integrated with a separately fabricated active-matrix-driving complementary metal-oxide semiconductor (CMOS) large-scale integration (LSI) system that controls each emitter individually. The basic function of the LSI was confirmed to receive external writing bitmap data and generate driving signals for turning beamlets on or off. Each emitted beamlet (10 × 10 μm2) is converged to 10 × 10 nm2 on a target via the reduction electron optic system under development. This paper presents an overview of the system and characteristic evaluations of the nc-Si emitter array. We examine beamlets and their electron emission characteristics via a 1:1 exposure test. Electron-beam lithography is becoming a crucial tool for semiconductor manufacturers that produce circuit patterns smaller than 10 nanometers. Masayoshi Esashi at Tohoku University, Japan, and colleagues chart their efforts to improve the low throughput level of this technique using arrays of nanocrystalline silicon electron emitters that emit thousands of ‘hot’ electron beams simultaneously. By integrating the electron-emitter array with an LSI, the team's Massively Parallel Electron Beam Direct Writing (MPEBDW) system can switch the beams on or off at high speed, similar to pixels in a computer display. The prototype uses a 100 × 100 emitter array and a reduction electron-optical system to converge the 100 × 100 pixels of 10 × 10 nanometers beams onto targets. This maskless method of nanoscale patterning makes MPEBDW less expensive and more flexible than conventional lithographic procedures.

Journal ArticleDOI
TL;DR: Ion Stiharu at Concordia University, Canada, and co-workers have developed a label-free approach that combines two portable microfluidic chips that separates cancer cells according to size and electric properties.
Abstract: The paper presents the principles and the results of the implementation of dielectrophoresis for separation and identification of rare cells such as circulation tumor cells (CTCs) from diluted blood specimens in media and further label-free identification of the origins of separated cells using radio-frequency (RF) imaging. The separation and the identification units use same fabrication methods which enable system integration on the same platform. The designs use the advantage of higher surface volume ratio which represents the particular feature for micro- and nanotechnologies. Diluted blood in solution of sucrose–dextrose 1–10 is used for cell separation that yields more than 95.3% efficiency. For enhanced sensitivity in identification, RF imaging is performed in 3.5–1 solution of glycerol and trypsin. Resonance cavity performance method is used to determine the constant permittivity of the cell lines. The results illustrated by the signature of specific cells subjected to RF imaging suggest a reliable label-free single cell detection method for identification of the type of CTC. Rapid, early detection of medical conditions that alter cell functions is imminent thanks to microfluidic single-cell analysis systems. Diagnosis and prognosis of various cancers hinge on the presence of tumor cells in the blood. Existing clinical methods rely on the use of high-affinity labels, such as antibodies or dye molecules, to monitor these rare cells, which can delay treatment. Ion Stiharu at Concordia University, Canada, and co-workers have developed a label-free approach that combines two portable microfluidic chips. The first platform separates cancer cells according to size and electric properties. Blood samples are subjected to a tunable, non-uniform electric field that moves target cells towards the electrodes, whereas their analogs remain in the field. In the second platform, the now-isolated target cells produce different radio frequency responses depending on their origin, which enables their identification.

Journal ArticleDOI
TL;DR: In this article, the authors demonstrate the layer-by-layer assembly of polyelectrolyte multilayers (PEM) on 3D nanofiber scaffolds for enhanced biomolecule isolation and detection.
Abstract: We demonstrate the layer-by-layer (LbL) assembly of polyelectrolyte multilayers (PEM) on three-dimensional nanofiber scaffolds. High porosity (99%) aligned carbon nanotube (CNT) arrays are photolithographically patterned into elements that act as textured scaffolds for the creation of functionally coated (nano)porous materials. Nanometer-scale bilayers of poly(allylamine hydrochloride)/poly(styrene sulfonate) (PAH/SPS) are formed conformally on the individual nanotubes by repeated deposition from aqueous solution in microfluidic channels. Computational and experimental results show that the LbL deposition is dominated by the diffusive transport of the polymeric constituents, and we use this understanding to demonstrate spatial tailoring on the patterned nanoporous elements. A proof-of-principle application, microfluidic bioparticle capture using N-hydroxysuccinimide-biotin binding for the isolation of prostate-specific antigen (PSA), is demonstrated. Nanoscale surface tailoring in 3D for enhanced biomolecule isolation and detection is now possible through layer-by-layer assembly. Next-generation biomedical applications — such as the capture and detection of biological markers at low concentrations — will depend on the systematic functionalization of the surfaces of tiny 3D scaffolds that are confined to intricate shapes. However, the application of existing surface modifications is restricted to planar structures and small particles. Brian Wardle and co-workers from the Massachusetts Institute of Technology, United States, have extended such modifications to complex porous materials. They patterned vertically aligned carbon nanotubes inside microfluidic devices then used successive depositions to produce high-porosity arrays with uniform and conformal coatings of nanoscale thickness and morphology. As proof-of-concept, the team used antibody-linked arrays to capture target antigens, demonstrating the versatility of the platform for future microfluidic applications.

Journal ArticleDOI
TL;DR: A new design for a microfluidic device that can perform continuousOptically induced electroporation (OIE) is developed, capable of automatically performing multiple gene transfections into mammalian cells and is suitable for handling small or rare cell populations.
Abstract: Optically induced electroporation (OIE) is a promising microfluidic-based approach for the electroporation of cell membranes. However, previously proposed microfluidic cell-electroporation devices required tedious sample pre-treatment steps, specifically, periodic media exchange. To enable the use of this OIE process in a practical protocol, we developed a new design for a microfluidic device that can perform continuous OIE; i.e., it is capable of automatically replacing the culture medium with electroporation buffers. Integrating medium exchanges on-chip with OIE minimises critical issues such as cell loss and damage, both of which are common in traditional, centrifuge-based approaches. Most importantly, our new system is suitable for handling small or rare cell populations. Two medium exchange modules, including a micropost array railing structure and a deterministic lateral displacement structure, were first adopted and optimised for medium exchange and then integrated with the OIE module. The efficacy of these integrated microfluidic systems was demonstrated by transfecting an enhanced green fluorescent protein (EGFP) plasmid into human embryonic kidney 293T cells, with an efficiency of 8.3%. This result is the highest efficiency reported for any existing OIE-based microfluidic system. In addition, successful co-transfections of three distinct plasmids (EGFP, DsRed and ECFP) into cells were successfully achieved. Hence, we demonstrated that this system is capable of automatically performing multiple gene transfections into mammalian cells. A microfluidic device offers a more streamlined approach for introducing foreign genes into mammalian cells. So-called ‘lab-on-a-chip’ systems could simplify and improve the efficiency of many biological techniques by employing microscale channels and valves to precisely control the movement of fluids, cells and reagents. Researchers led by Gwo-Bin Lee of National Tsing Hua University, Hsinchu, have devised such a system to manage the targeted genetic modification of cultured cells via a process known as electroporation. Lee and colleagues constructed microfluidic devices that employ polymeric structures to direct a continuously flowing stream of cells out of their culture medium and into a specialized module for light-induced electroporation. Their approach achieves remarkable efficiency in introducing individual genes into human cells, and the researchers were even able to use their device to deliver three different plasmids simultaneously.

Journal ArticleDOI
TL;DR: Papakayala et al. as discussed by the authors presented passive, wireless, resonant magnetoelastic actuators intended for the generation of fluid flow on the surfaces of implantable Ahmed glaucoma drainage devices.
Abstract: Magnetoelastic resonators made from metal alloy foils are widely used for miniature wireless anti-theft tags and have also been explored for use in various sensing applications. Through annealing within three-dimensional (3D) molds, these foils can be formed into curved structures. Consequently, magnetoelastic materials present an opportunity for the development of a new class of wireless, actuators that have small form factors and low surface profiles and that can conform to curved surfaces. This paper describes passive, wireless, resonant magnetoelastic actuators intended for the generation of fluid flow on the surfaces of implantable Ahmed glaucoma drainage devices. The actuators are remotely excited to resonance using a magnetic field generated by external coils. The fluid flow is intended to limit cellular adhesion to the surface of the implant, as this adhesion can ultimately lead to implant encapsulation and failure. The actuators are micromachined from planar 29-μm-thick foils of Metglas 2826MB (Fe40Ni38Mo4B18), an amorphous magnetoelastic alloy, using photochemical machining. Measuring 10.3 × 5.6 mm2, the planar structures are annealed in 3D molds to conform to the surface of the drainage device, which has an aspherical curvature. Six actuator designs are described, with varying shapes and resonant mode shapes. The resonant frequencies for the different designs vary from 520 Hz to 4.7 kHz. Flow velocities of up to 266 μm s−1 are recorded at a wireless activation range of 25–30 mm, with peak actuator vibration amplitudes of 1.5 μm. Integrated actuators such as those described here have the potential to greatly enhance the effectiveness of glaucoma drainage devices at lowering eye pressure and may also be useful in other areas of medicine. Implantable microstructures that respond to magnetic stimulation could transform therapy for the eye disease glaucoma. In this condition, fluid accumulation builds pressure that damages the optic nerve and induces blindness. As an alternative to conventional treatment with pharmaceuticals or laser surgery, drainage implants relieve the pressure by releasing excess fluid through a tube. However, over time these implants become clogged by fibrous cells. To alleviate such fouling, Venkatram Pepakayala and co-workers from the University of Michigan, USA, have developed thin metal alloy objects that vibrate under the action of an oscillating magnetic field. Thermally curved to conform to the biodevice, these objects can be embedded in the eye with the implant then activated using a toothbrush-sized magnet. Preliminary assessments demonstrate their ability to create vibrations in water that can prevent cell adhesion and proliferation.

Journal ArticleDOI
TL;DR: Osuji et al. as discussed by the authors developed a generalized method to overcome this limitation by sacrificial template imprinting using zinc oxide (ZnO) nanostructures, which can be grown inexpensively and quickly with tunable morphologies on a wide variety of substrates out of solution, which exploit to generate the nanoscale portion of the multiscale pattern through this bottom-up approach.
Abstract: Bulk metallic glasses (BMGs) have been developed as a means to achieve durable multiscale, nanotextured surfaces with desirable properties dictated by topography for a multitude of applications. One barrier to this achievement is the lack of a bridging technique between macroscale thermoplastic forming and nanoimprint lithography, which arises from the difficulty and cost of generating controlled nanostructures on complex geometries using conventional top-down approaches. This difficulty is compounded by the necessary destruction of any resulting reentrant structures during rigid demolding. We have developed a generalized method to overcome this limitation by sacrificial template imprinting using zinc oxide (ZnO) nanostructures. It is established that such structures can be grown inexpensively and quickly with tunable morphologies on a wide variety of substrates out of solution, which we exploit to generate the nanoscale portion of the multiscale pattern through this bottom-up approach. In this way, we achieve metallic structures that simultaneously demonstrate features from the macroscale down to the nanoscale, requiring only the top-down fabrication of macro/microstructured molds. Upon detachment of the formed part from the multiscale molds, the ZnO remains embedded in the surface and can be removed by etching in mild conditions to both regenerate the mold and render the surface of the BMGs nanoporous. The ability to pattern metallic surfaces in a single step on length scales from centimeters down to nanometers is a critical step toward fabricating devices with complex shapes that rely on multiscale topography for their intended functions, such as biomedical and electrochemical applications. Biomedical and optical devices stand to benefit from a multiscale patterning technique developed by researchers in the USA. Bulk metallic glasses (BMGs) are extremely strong and corrosion-resistant alloys that can be thermoplastically molded with features spanning centimeter to nanometer dimensions. The generation of multiscale molds with conventional lithography, however, requires several costly steps. To simplify BMG patterning from the bottom-up, Chinedum Osuji from Yale University and co-workers from Yale and Rutgers grew tunably packed nanowires and nanosheets of zinc oxide (ZnO) directly onto mold surfaces. When a BMG is formed then detached from this modified mold, the nanostructures embed themselves into the metallic surface. A subsequent mild etching procedure removes the ZnO and gives the BMG a nanoporous surface—an economical route to biomimetic textures for applications ranging from biomanipulation to fuel cells.

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TL;DR: A flat microscopic device that—under the guidance of a pneumatic balloon—arranges into an intestine-like tube with an easy-to-examine interior that shows realistic adsorption behavior toward model drugs.
Abstract: Whole animal studies for monitoring drug flow into the body may be consigned to the past, thanks to artificial intestines. During drug development, animal studies play a pivotal role in ensuring drug effectiveness and safety before clinical trials in humans. More recently, alternative, in vitro, strategies using cultured cells and tissues combined with microchip technologies have emerged as more humane substitutes for such procedures. However, these experiments typically rely on planar supports for cell growth instead of lifelike, three-dimensional scaffolds—skewing pharmacological tests. Now, Satoshi Konishi and co-workers from Ritsumeikan University, Japan, have created a flat microscopic device that—under the guidance of a pneumatic balloon—arranges into an intestine-like tube with an easy-to-examine interior. When used as a support for intestinal cells in culture, the device shows realistic adsorption behavior toward model drugs.

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TL;DR: A novel two-stage, stopped-flow, continuous centrifugal sedimentation strategy to measure the size distributions of events (defined here as cells or clusters thereof) in a blood sample and shows that the occupancy distribution of the collection bins closely correlates with the range of cluster sizes intrinsic to the specific cell line.
Abstract: There is increasing evidence that, in addition to their presence, the propensity of circulating tumour cells to form multi-cellular clusters bears significant information about both cellular resistance to chemotherapy and overall prognosis. We present a novel two-stage, stopped-flow, continuous centrifugal sedimentation strategy to measure the size distributions of events (defined here as cells or clusters thereof) in a blood sample. After off-chip removal of red blood cells, healthy white blood cells are sequestered by negative-immunocapture. The purified events are then resolved along a radially inclined rail featuring a series of gaps with increasing width, each connected to a designated outer collection bin. The isolation of candidate events independent of target-specific epitopes is successfully demonstrated for HL60 (EpCAM positive) and sk-mel28 (EpCAM negative) cells using identical protocols and reagents. The propensity to form clusters was quantified for a number of cell lines, showing a negligible, moderate or elevated tendency towards cluster formation. We show that the occupancy distribution of the collection bins closely correlates with the range of cluster sizes intrinsic to the specific cell line. Simultaneous isolation and quantification of individual cells and cell clusters is possible thanks to a centrifugal sedimentation approach. Tumor cells circulating in the blood are an excellent indicator for the prognosis of various cancers. In particular, the presence of tumor-cell clusters enhances the risk of metastasis in patients. Although microfluidic lab-on-a-chip systems designed to isolate individual cells can sometimes resolve such clusters, a subsequent step is required to quantify the cluster load of the sample. Now, Jens Ducree and co-workers from Dublin City University, Ireland, have created a microfluidic chamber that integrates cell separation and quantification steps. By centrifugation through an inclined rail featuring a series of concentric, increasingly wider gaps, cells and clusters deposit into bins for particles of predetermined sizes. Their presence in any bin can then be determined using simple microscopy techniques.

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TL;DR: Mayr et al. as mentioned in this paper combined the advantages of NIR excitation and far-red emissive indicator dyes, offering minimized auto-fluorescence and enhanced membrane permeability.
Abstract: Oxygen sensing, magnetic, and upconversion luminescence properties are combined in multi-functional composite particles prepared herein by a simple mixing, baking, and grinding procedure. Upconverting nanocrystals are used as an excitation source and an oxygen indicator with far-red emission. The composite particles are excited with near infrared (NIR) laser light (980 nm). The visible upconversion emission is converted into an oxygen concentration-dependent far-red emission (<750 nm) using an inert mediator dye and a platinated benzoporphyrin dye. This concept combines the advantages of NIR excitation and far-red emissive indicator dyes, offering minimized auto-fluorescence and enhanced membrane permeability. Additional functionality is obtained by incorporating magnetic nanoparticles into the composite particles, which enables easy manipulation and separation of the particles by the application of an external magnetic field. Researchers from Austria and Germany have synthesized a composite of optical nanometer material particles that enable measurement of the amount of oxygen in a system. Torsten Mayr and colleagues from the Graz University of Technology and the University of Regensburg combine a light-emitting dye with inorganic nanoparticles that contain traces of erbium and ytterbium atoms. The composite particles absorb incoming near-infrared light and re-emit it at a shorter wavelength in the far red. The efficiency of this process, known as upconversion, is dependent on the concentration of oxygen in the environment. Such an optical oxygen sensor has the advantages of being contactless and non-invasive. In addition, the re-emitted far-red light is not reabsorbed or scattered by biological matter. The concept could therefore find applications in medical diagnostics and biotechnology research.


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TL;DR: The First Engineering Journal from Nature Publishing Group: Microsystems & Nanoengineering
Abstract: The First Engineering Journal from Nature Publishing Group: Microsystems & Nanoengineering