Activity of the integrated on-line trypsin microreactor and nanoelectrospray emitter in acetonitrile–water co-solvent mixtures

The on-line trypsin microreactor and nanoelectrospray emitter for peptide mass mapping was demonstrated to be functional under aqueous conditions, but it is well known that electrospray ionization works more efficiently with organic co-solvents. Here, an activity assay was developed to determine the activity of this integrated device with acetonitrile as a co-solvent. Trypsin was immobilized onto fused silica capillaries pulled to fine tips as integrated microreactors coupled as nanoelectrospray ionization emitters. The model substrate N _α-benzoyl-l-arginine ethyl ester (2.5–20 μM) and an internal standard (N _α-Z-l-arginine (Z-Arg)) were dissolved in acetonitrile/water at various ratios and infused through the immobilized trypsin microreactor. The trypsin digestion product N _α-benzoyl-l-arginine (B-Arg) was detected by nanoelectrospray ionization coupled to an ion trap mass spectrometer, and its abundance compared to Z-Arg for quantification. The activity of immobilized trypsin in the microreactor was determined by measuring the ratio of the peak intensities of the hydrolysis product B-Arg to Z-Arg internal standard (three replicates). Kinetic parameters determined from Lineweaver–Burk analysis indicate an enhancement of trypsin activity upon immobilization and the addition of increasing ratios of acetonitrile up to 80 %, where K _m is 0.14 mM and V _max = 1.2 μM/s. Much lower immobilized trypsin activities were noted at 100 % ammonium acetate or 100 % acetonitrile than when the two solvents were mixed. The results clearly indicate that immobilized trypsin retains high biocatalytic activity in 20–80 % acetonitrile and is highly compatible with nanoelectrospray ionization mass spectrometry.     

Two-axis micro fluxgate sensor on single chip

We present a two-axis micro fluxgate sensor on single chip for electronic compassing function. To measure X- and Y-axis magnetic fields, functional two fluxgate sensors were perpendicularly aligned and connected each other. The fluxgate sensor was composed of square-ring shaped magnetic core and solenoid excitation and pick-up coils. The solenoid coils and magnetic core were separated by benzocyclobutane which had high insulation and good planarization characters. Copper coil patterns of 10 μm width and 6 μm thickness were electroplated on Ti (300 Å)/Cu (1,500 Å) seed layers. 3 μm thick Ni_0.8Fe_0.2 (permalloy) film for the magnetic core was also electroplated under 2,000 gauss. Excellent linear response over the range of ?100 μT to +100 μT was obtained with the sensitivity of ～280 V/T. Actual chip size was 3.1×3.1 mm². The sine and cosine signals of two-axis fluxgate sensor had a good function of azimuth compass.     

Fabrication of 1D nanochannels on thermoplastic substrates using microchannel compression

We present a new method to fabricate one-dimensional (1D) nanochannels on a thermoplastic substrate. This method has two main steps. First, a mold with microscale features is used to replicate microchannels on a thermoplastic substrate. Second, the fabricated microchannel is compressed to a 1D nanochannel at a temperature above the glass transition temperature (T_g) of the themoplastics. The effects of compression temperature, compression pressure, retaining time and loading rate on microchannel compression have been studied. Results have shown that a 1D nanochannel of 1–30 μm wide and 200–300 nm deep can be readily fabricated by using this method.     

Development and characterization of a microthermoelectric generator with plated copper/constantan thermocouples

This work reports the development and the characterization of a microthermoelectric generator (μTEG) based on planar technology using electrochemically deposited constantan and copper thermocouples on a micro machined silicon substrate with a SiO₂/Si₃N₄/SiO₂ thermally insulating membrane to create a thermal gradient. The μTEG has been designed and optimized by finite element simulation in order to exploit the different thermal conductivity of silicon and membrane in order to obtain the maximum temperature difference on the planar surface between the hot and cold junctions of the thermocouples. The temperature difference was dependent on the nitrogen (N₂) flow velocity applied to the upper part of the device. The fabricated thermoelectric generator presented maximum output voltage and power of 118 mV/cm² and of 1.1 μW/cm², respectively, for a device with 180 thermocouples, 3 kΩ of internal resistance, and under a N₂ flow velocity of 6 m/s. The maximum efficiency (performance) was 2 × 10^?3 μW/cm² K².     

Numerical simulation of the capillary flow in the meander microchannel

Pumping in microfluidic devices is an important issue in actuating fluid flow in microchannel, especially that capillary force has received more and more attractions due to the self-driven motion without external power input. However, less 2D simulation was done on the capillary flow in microchannel especially the meander microchannel which can be used for mixing and lab-on-a-chip (LOC) application. In this paper, the numerical simulation of the capillary flow in the meander microchannel has been studied using computer fluid dynamic simulation software CFD-ACE⁺. Different combinations of channel width in the X-direction denoted as W_x and Y-direction denoted as W_y were designed for simulating capillary flow behavior and pressure drop. The designed four types of meander microchannels (W_x × W_y) were 100 × 100 μm, 100 × 200 μm, 50 × 200 μm, and 50 × 400 μm. In this simulation results, it is found that the capillary pumping speed is highly depending on the channel width. The large speed change occurs at the turning angle of channel width change from W_x to W_y. The fastest pumping effect is found in the meander channel of 100 × 100 μm, which has an average pumping speed of 0.439 mm/s. The slowest average flow speed of 0.205 mm/s occurs in the meander channel of 50 × 400 μm. Changing the meander channel width may vary the capillary flow behavior including the pumping speed and the flow resistance as well as pressure drop which will be a good reference in designing the meander microchannels for microfluidic and LOC application.     

Driving characteristics of the electrowetting-on-dielectric device using atomic-layer-deposited aluminum oxide as the dielectric

Electrowetting on dielectric (EWOD) is useful in manipulating droplets for digital (droplet-based) microfluidics, but its high driving voltage over several tens of volts has been a barrier to overcome. This article presents the characteristics of EWOD device with aluminum oxide (Al₂O₃, ε _r  ≈ 10) deposited by atomic layer deposition (ALD), for the first time as the high-k dielectric for lowering the EWOD driving voltage substantially. The EWOD device of the single-plate configuration was fabricated by several steps for the control electrode array of 1 mm × 1 mm squares with 50 μm space, the dielectric layer of 1,270 Å thick ALD Al₂O₃, the reference electrode of 20 μm wide line electrode, and the hydrophobic surface treatment by Teflon-AF coating, respectively. We observed the movement of a 2 μl water droplet in an air environment, applying a voltage between one of the control electrodes and the reference electrode in contact with the droplet. The droplet velocity exponentially depending on the applied voltage below 15 V was obtained. The measured threshold voltage to move the droplet was as low as 3 V which is the lowest voltage reported so far in the EWOD researches. This result opens a possibility of manipulating droplets, without any surfactant or oil treatment, at only a few volts by EWOD using ALD Al₂O₃ as the dielectric.     

Manufacture of microfluidic glass chips by deep plasma etching, femtosecond laser ablation, and anodic bonding

Two dry subtractive techniques for the fabrication of microchannels in borosilicate glass were investigated, plasma etching and laser ablation. Inductively coupled plasma reactive ion etching was carried out in a fluorine plasma (C₄F₈/O₂) using an electroplated Ni mask. Depth up to 100 μm with a profile angle of 83°–88° and a smooth bottom of the etched structure (Ra below 3 nm) were achieved at an etch rate of 0.9 μm/min. An ultrashort pulse Ti:sapphire laser operating at the wavelength of 800 nm and 5 kHz repetition rate was used for micromachining. Channels of 100 μm width and 140 μm height with a profile angle of 80–85° were obtained in 3 min using an average power of 160 mW and a pulse duration of 120 fs. A novel process for glass–glass anodic bonding using a conductive interlayer of Si/Al/Si has been developed to seal microfluidic components with good optical transparency using a relatively low temperature (350°C).     

Submicron polymer structures with X-ray lithography and hot embossing

This article describes the process chain for replication of submicron structures with varying aspect ratios (AR) up to 6 in polymethylmethacrylate (PMMA) by hot embossing to show the capability of the entire LIGA process to fabricate structures with these dimensions. Therefore a 4.7 μm thick layer of MicroChem 950k PMMA A11 resist was spin-coated on a 2.3 μm Ti/TiO _x membrane. It was patterned with X-ray lithography at the electron storage ring ANKA (2.5 GeV and λ _c ≈ 0.4 nm) at a dose of 4 kJ/cm³ using a Si₃N₄ membrane mask with 2 μm thick gold-absorbers. The samples were developed in GG/BDG and resulted in AR of 6–14. Subsequent nickel plating at 52°C resulted in a 200 μm thick nickel tool of 100 mm diameter, which was used to replicate slit-nozzles and columns in PMMA. Closely packed submicron cavities with AR 6 in the nickel shim were filled to 60% during hot embossing.     

Research on angle of the failure cone of lightweight nanoceramic/metal laminated composite in the impact test

Lightweight laminated composites containing a ceramic front layer and a metallic backing layer were used in order to protect people, moving equipment and mobile vehicles from high velocity impact and the increased mobility of mobile vehicles. In this study, by adding 10 vol% SiC and 500 ppm MgO nanoscale particles on the microstructure of Al₂O₃ matrix and applying optimum sintering conditions, ceramic performance against high-speed projectile impact was improved. To perform this investigation, a number of specimens with two different types of front layers (alumina and Al₂O₃–SiC–MgO nanocomposite ceramic) were produced. Impact tests were conducted on these samples using 7.62 mm projectiles with a velocity of 820 ± 15 m/s. The diameter of the base of failure cone after impact tests was measured. The results of the impact tests on the samples made of Al₂O₃–SiC–MgO nanocomposite ceramics and pure alumina were also compared and analysed. The results indicate that measured diameter of the base of failure cone after impact test for all ceramic nanocomposites is more than raw specimen and increasing in the diameter of the base of failure cone is related to increasing of the angle of failure cone.     

H<Subscript>2</Subscript>S nano-jetting through a p–n junction-like graphene/Au nano-injector: a molecular dynamics study

This paper uses fully atomistic molecular dynamics to outline the dynamics of H₂S nano-jetting through a p–n junction-like graphene/Au nano-injector. We examined the effects of nano-injector diameter (d), system temperature (T), and the extrusion velocity (v) of a graphite piston plate on the formation of H₂S nano-jets, system pressure, and the number of molecules (N _m) in the outflow. The combined effects of high critical pressure and small orifice resulted in a larger jet angle, which increased the number of H₂S molecules stuck to the graphene surface at the outlet. Moving the graphite piston plate toward the orifice of the nano-injector increased in the change in momentum and interactive forces between H₂S molecules, resulting in three phases of pressure establishment in the nano-injector: incubation (phase I), steep pressure increase (phase II), and high pressure (phase III). When operated at T ≥ 300 K and v < 27.912 m/s, the proposed nano-jet device is able to produce a well-dispersed spray of H₂S without H₂S molecules sticking to the graphene surface at the outlet. The p–n junction-like Au-doped graphene surface provides an additional energy barrier preventing the transport of electrons from H₂S molecule to the graphene. This inhibits the accumulation of H₂S molecules and subsequent blockages at the exit of the nano-injector. Simulation results demonstrate the potential of using chemiresistive sensing to monitor H₂S flow patterns during nano-jetting. The findings presented in this study could be transformative to the design of nano-injectors for other gases commonly used as biomarkers.     

Resist-less patterning on SiO2 by combination of X-ray exposure and vapor HF etching

We succeeded in a resist-less patterning of SiO₂/Si substrates by a combination of X-ray exposure and vapor hydrogen fluoride (HF) etching. A 2 μm thick SiO₂ layer was formed on a Si substrate by employing a thermal oxidation process. An X-ray mask consisted of a 1 μm thick Ta absorber on a 2 μm thick Si₃N₄ membrane mounted on a 1 mm thick Si frame, and a honeycomb pattern where 640 nm diameter circle dots arranged in the corners of a hexagon with a pitch of 960 nm was processed. X-ray exposure experiments were carried out on a beamline BL-4 with a peak photon energy of 2 keV at the TERAS synchrotron radiation (SR) facility. When a dose energy was 750 mAh, the transfer of the patterns was confirmed, although irradiations with different dose energy were also conducted. Moreover, heating temperatures and total etching times of SiO₂/Si substrates in vapor HF etching were changed, and the shapes of etched patterns were observed by scanning electron microscope. It was learnt that an appropriate etching time existed between 30 and 60 min. Moreover, we observed discoloration of irradiated area by SR; and this seemed to be caused by changes in the etching rate of SiO₂/Si substrates that led to the development of resist-less patterning technique.     

A facile strategy to integrate robust porous aluminum foil into microfluidic chip for sorting particles

High efficiency integration of functional microdevices into microchips is crucial for broad microfluidic applications. Here, a device-insertion and pressure sealing method was proposed to integrate robust porous aluminum foil into a microchannel for microchip functionalization which demonstrate the advantage of high efficient foil microfabrication and facile integration into the microfluidic chip. The porous aluminum foil with large area (10 × 10 mm²) was realized by one-step femtosecond laser perforating technique within few minutes and its pores size could be precisely controlled from 3 μm to millimeter scale by adjusting the laser pulse energy and pulse number. To verify the versatility and flexibility of this method, two kinds of different microchips were designed and fabricated. The vertical-sieve 3D microfluidic chip can separate silicon dioxide (SiO₂) microspheres of two different sizes (20 and 5 μm), whereas the complex stacking multilayered structures (sandwich-like) microfluidic chip can be used to sort three different kinds of SiO₂ particles (20, 10 and 5 μm) with ultrahigh separation efficiency of more than 92%. Furthermore, these robust filters can be reused via cleaning by backflow (mild clogging) or disassembling (heavy clogging).     

Size effect on mechanical properties of TiO2 capped nanotubes investigated using in situ transmission electron microscopy

In situ transmission electron microscopy nanoindentation tests are used to measure the compressive fracture and mechanical properties of individual titanium oxide (TiO₂) capped nanotubes. The average critical loads ranged from 3.6 to 9.6 μN. Individual TiO₂ capped nanotubes with lengths of 8–10 μm were found to have Young’s modulus values of ~2.2–9.4 GPa and work energy values of ~3.1–6.6 × 10^?13 J. The results indicate that the Young’s modulus and tensile strength depend on capped nanotube length.     

Fabrication of symmetrical meandering NiFe/Cu/NiFe film sensors and study of the effects of field direction and film thickness on giant magnetoimpedance

Sandwich NiFe/Cu/NiFe film sensors with symmetrical meandering structure are fabricated by Micro-Electro-Mechanical-System (MEMS) technology, the longitudinal, transverse, and perpendicular giant magnetoimpedance (GMI) effect have been investigated comprehensively. The correlation between film thickness and GMI effect are analyzed thoroughly. The experimental results show that the alternating current (AC) frequency of maximum GMI ratio decreases gradually with the increasing of magnetic layer thickness, but the conducting layer exhibits an opposite tendency. The NiFe and Cu layer both show a GMI ratio tendency from increasing to decreasing along with the increase of film thickness. It is observed the longitudinal, transverse and perpendicular GMI effect share a common characteristic: the AC frequency of maximum GMI ratio increases with the increase of external field intensity. However, there is a notable difference between them, it is demonstrated that the higher GMI ratio and sensitivity can be obtained in the longitudinal direction. The longitudinal GMI ratio reaches the peak value 191.2 % at f _AC = 6.5 MHz under H _L = 17 Oe in six turns sample with the Cu and NiFe thickness of 6 and 7 μm, respectively.     

Study on TSV isolation liners for a Via Last approach with the use in 3D-WLP for MEMS

This paper discusses approaches for the isolation of deep high aspect ratio through silicon vias (TSV) with respect to a Via Last approach for micro-electro-mechanical systems (MEMS). Selected TSV samples have depths in the range of 170…270 µm and a diameter of 50 µm. The investigations comprise the deposition of different layer stacks by means of subatmospheric and plasma enhanced chemical vapour deposition (PECVD) of tetraethyl orthosilicate; Si(OC₂H₅)₄ (TEOS). Moreover, an etch-back approach and the selective deposition on SiN were also included in the investigations. With respect to the Via Last approach, the contact opening at the TSV bottom by means of a specific spacer-etching method have been addressed within this paper. Step coverage values of up to 74 % were achieved for the best of those approaches. As an alternative to the SiO₂-isolation liners a polymer coating based on the CVD of Parylene F was investigated, which yields even higher step coverage in the range of 80 % at the lower TSV sidewall for a surface film thickness of about 1000 nm. Leakage current measurements were performed and values below 0.1 nA/cm² at 10 kV/cm were determined for the Parylene F films which represents a promising result for the aspired application to Via Last MEMS-TSV.     

Alterations in the complex refractive index of copper oxide thin films as sensing effect for hydrogen sulfide monitoring

Throughout the last three decades cuprous (Cu₂O) and cupric oxide (CuO) have been subject of extensive investigations of their material properties. This research was mainly driven by potential applicability as a photovoltaic or doping material. However, CuO/Cu₂O layers show a specific reaction towards hydrogen sulfide (H₂S), making it a good candidate as highly selective gas sensor material. On this account thin film samples of CuO and Cu₂O have been investigated with regard to their specific surface interactions with H₂S gas. Changes in morphology, chemical composition, and alterations in the complex refractive index have been thoroughly examined in order to understand possible sensing effects. Raman spectroscopy was used for verifying the films composition after heat treatment. Transmission and reflection characteristics in the extended UV/Vis regime (350–1,100 nm) of initially prepared samples and after exposure to well-defined doses of H₂S were recorded. A distinct increase in transmissivity was observed for Cu₂O films in the wavelength region λ = 550–900 nm. An initial conditioning effect was observed from consecutive measurements. Absorptivity characteristics and optical band gaps were derived, showing an absorptivity shift of CuO thin films after exposure towards H₂S. A specific optical read-out based on total internal reflection was set-up, offering a transient monitoring of the materials surface interactions with the gas phase. Changes in the response, in terms of intensity variations, were reproducibly shown for low concentrations of 5 ppm of H₂S.     

Monolithic integration of Pb(Zr,Ti)O3 thin film based resonators using a complete dry microfabrication process

Monolithic fabrication of lead zirconate titanate [Pb(Zr,Ti)O₃ or PZT] based thin film resonant devices such as microcantilevers, Lamb wave and bulk acoustic wave resonators are demonstrated. High-performance PZT thin films with a thickness of 2.6 μm are prepared on a silicon on insulator wafer by a sputtering deposition process. A highly selective reactive ion etching process is employed for micro-patterning of PZT, platinum electrodes, and SiO₂ insulation layer. Self-actuation of the PZT microcantilevers is demonstrated and the frequency response is characterized using a laser Doppler vibrometer. The frequency response of the Lamb wave resonator is evaluated by measuring its transmission characteristic using a network analyzer. For a Lamb wave resonator with a length of 240 μm and an interdigital period of 80 μm, the 1st order and 2nd resonance frequencies are 15.3 and 41.8 MHz, respectively.     

Micromachined ultrasonic transducers based on lead zirconate titanate (PZT) films

The design, fabrication and measuring of piezoelectric micromachined ultrasonic transducers (pMUTs), including the deposition and patterning of PZT films, was investigated. The (100) preferential orientation of PZT film have been deposited on Pt/Ti/SiO₂/Si (100) substrates by modified sol–gel method. PZT film and Pt/Ti electrode were patterned by novel lift-off using ZnO as a sacrificial layer avoiding shortcomings of dry and wet etching methods. pMUT elements have been fabricated by an improved silicon micromachining process and their properties were also characterized. As measured results, the pMUT tends to operate in a standard plate-mode. The receive sensitivity and transmit sensitivity of pMUT element whose active area only has 0.25 mm² are ?218 dB (ref. 1 V/μPa) and 139 dB (ref. 1 μPa/V), respectively.     

On-chip manipulation and trapping of microorganisms using a patterned magnetic pathway

We demonstrate on-chip manipulation and trapping of individual microorganisms at designated positions on a silicon surface within a microfluidic channel. Superparamagnetic beads acted as microorganism carriers. Cyanobacterium Synechocystis sp. PCC 6803 microorganisms were immobilized on amine-functionalized magnetic beads (Dynabead^® M-270 Amine) by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)–N-hydroxysulfosuccinimide coupling chemistry. The magnetic pathway was patterned lithographically such that half-disk Ni₈₀Fe₂₀ (permalloy) 5 μm elements were arranged sequentially for a length of 400 micrometers. An external rotating magnetic field of 10 mT was used to drive a translational force (maximum 70 pN) on the magnetic bead carriers proportional to the product of the field strength and its gradient along the patterned edge. Individual microorganisms immobilized on the magnetic beads (transporting objects) were directionally manipulated using a magnetic rail track, which was able to manipulate particles as a result of asymmetric forces from the curved and flat edges of the pattern on the disk. Transporting objects were then successfully trapped in a magnetic trapping station pathway. The transporting object moves two half-disk lengths in one field rotation, resulting in movement at ~24 μm s^?1 for 1 Hz rotational frequency with 5 μm pattern elements spaced with a 1 μm gap between elements.     

Micro injection molding for mass production using LIGA mold inserts

Micro molding is one of key technologies for mass production of polymer micro parts and structures with high aspect ratios. The authors developed a commercially available micro injection molding technology for high aspect ratio microstructures (HARMs) with LIGA-made mold inserts and pressurized CO₂ gasses. The test inserts made of nickel with the smallest surface details of 5 μm with structural height of 15 μm were fabricated by using LIGA technology. High surface quality in terms of low surface roughness of the mold inserts allowed using for injection molding. Compared to standard inserts no draft, which is required to provide a proper demolding, was formed in the inserts. To meet higher economic efficiency and cost reduction, a fully electrical injection molding machine of higher accuracy has been applied with dissolving CO₂ gasses into molten resin. The gasses acts as plasticizer and improves the flowability of the resin. Simultaneously, pressurizing the cavity with the gasses allows high replication to be obtained. Micro injection molding, using polycarbonate as polymer resins, with the aspect ratio of two was achieved in the area of 28 × 55 mm² at the cycle time of 40 s with CO₂ gasses, in contrast to the case of the aspect ratio of 0.1 without the gasses.