Micromachines, Volume 7, Issue 6 (June 2016) – 13 articles

Compound process technology has been investigated for many years on a macro scale, but only a few studies can be found on a micro scale due to the difficulties in tool manufacturing, parts transporting and punch-die alignment. In this paper, a novel technology of combining the laser shock wave and soft punch was introduced to fabricate the dish-shaped micro-parts on copper to solve these difficulties. This compound process includes deep drawing, punching and blanking and these processes can be completed almost at the same time because the duration time of laser is quite short, so the precision of the micro-parts can be ensured. A reasonable laser energy of 1550 mJ made the morphology, depth of deformation, dimensional accuracy and surface roughness achieve their best results when the thickness of the soft punches was 200 μm. In addition, thicker soft punches may hinder the compound process due to the action of unloading waves based on the elastic wave theory. So, the greatest thickness of the soft punches was 200 μm. Full article

Robot-assisted cell manipulation is gaining attention for its ability in providing high throughput and high precision cell manipulation for the biological industry. This paper presents a visual servo microrobotic system for cell microinjection. We investigated the automatic cell autofocus method that reduced the complexity of the system. Then, we produced an adaptive visual processing algorithm to detect the location of the cell and micropipette toward the uneven illumination problem. Fourteen microinjection experiments were conducted with zebrafish embryos. A 100% success rate was achieved either in autofocus or embryo detection, which verified the robustness of the proposed automatic cell manipulation system. Full article

Cadmium(II) is a common water pollutant with high toxicity. It is of significant importance for detecting aqueous contaminants accurately, as these contaminants are harmful to human health and environment. This paper describes the fabrication, characterization, and application of an environment-friendly graphene (Gr)/l-cysteine/gold electrode to detect trace levels of cadmium (Cd) by differential pulse stripping voltammetry (DPSV). The influence of hydrogen overflow was decreased and the current response was enhanced because the modified graphene extended the potential range of the electrode. The Gr/l-cysteine/gold electrode showed high electrochemical conductivity, producing a marked increase in anodic peak currents (vs. the glass carbon electrode (GCE) and boron-doped diamond (BDD) electrode). The calculated detection limits are 1.15, 0.30, and 1.42 µg/L, and the sensitivities go up to 0.18, 21.69, and 152.0 nA·mm⁻²·µg⁻¹·L for, respectively, the BDD electrode, the GCE, and the Gr/l-cysteine/gold electrode. It was shown that the Gr/l-cysteine/gold-modified electrode is an effective means for obtaining highly selective and sensitive electrodes to detect trace levels of cadmium. Full article

Optofluidics is a rapidly growing versatile branch of adaptive optics including a wide variety of applications such as tunable beam shaping tools, mirrors, apertures, and lenses. In this review, we focus on recent developments in optofluidic lenses, which arguably forms the most important part of optofluidics devices. We report first on a number of general characteristics and characterization methods for optofluidics lenses and their optical performance, including aberrations and their description in terms of Zernike polynomials. Subsequently, we discuss examples of actuation methods separately for spherical optofluidic lenses and for more recent tunable aspherical lenses. Advantages and disadvantages of various actuation schemes are presented, focusing in particular on electrowetting-driven lenses and pressure-driven liquid lenses that are covered by elastomeric sheets. We discuss in particular the opportunities for detailed aberration control by using either finely controlled electric fields or specifically designed elastomeric lenses. Full article

Acoustophoresis is a technique that applies ultrasonic standing wave forces in a microchannel to sort cells depending on their physical properties in relation to the surrounding media. Cell handling and separation for research and clinical applications aims to efficiently separate specific cell populations. Here, we investigated the sorting of CD8 lymphocytes from peripheral blood progenitor cell (PBPC) products by affinity-bead-mediated acoustophoresis. PBPC samples were obtained from healthy donors (n = 4) and patients (n = 18). Mononuclear cells were labeled with anti-CD8-coated magnetic beads and sorted on an acoustophoretic microfluidic device and by standard magnetic cell sorting as a reference method. CD8 lymphocytes were acoustically sorted with a mean purity of 91% ± 8% and a median separation efficiency of 63% (range 15.1%–90.5%) as compared to magnetic sorting (purity 91% ± 14%, recovery 29% (range 5.1%–47.3%)). The viability as well as the proliferation capacity of sorted lymphocytes in the target fraction were unimpaired and, furthermore, hematopoietic progenitor cell assay revealed a preserved clonogenic capacity post-sorting. Bead-mediated acoustophoresis can, therefore, be utilized to efficiently sort less frequent CD8+ lymphocytes from PBPC products in a continuous flow mode while maintaining cell viability and functional capacity of both target and non-target fractions. Full article

Low flow rate micropumps play an increasingly important role in drug therapy research. Infusions to small biological structures and lab-on-a-chip applications require ultra-low flow rates and will benefit from the ability to expend no power in the blocked-flow state. Here we present a planar micropump based on gallium phase-change actuation that leverages expansion during solidification to occlude the flow channel in the off-power state. The presented four chamber peristaltic micropump was fabricated with a combination of Micro Electro Mechanical System (MEMS) techniques and additive manufacturing direct write technologies. The device is 7 mm × 13 mm × 1 mm (<100 mm³) with the flow channel and exterior coated with biocompatible Parylene-C, critical for implantable applications. Controllable pump rates from 18 to 104 nL/min were demonstrated, with 11.1 ± 0.35 nL pumped per actuation at an efficiency of 11 mJ/nL. The normally-closed state of the gallium actuator prevents flow and diffusion between the pump and the biological system or lab-on-a-chip, without consuming power. This is especially important for implanted applications with periodic drug delivery regimens. Full article

We report multi-responsive and double-folding bilayer hydrogel sheet actuators, whose directional bending response is tuned by modulating the solvent quality and temperature and where locally crosslinked regions, induced by ionoprinting, enable the actuators to invert their bending axis. The sheets are made multi-responsive by combining two stimuli responsive gels that incur opposing and complementary swelling and shrinking responses to the same stimulus. The lower critical solution temperature (LCST) can be tuned to specific temperatures depending on the EtOH concentration, enabling the actuators to change direction isothermally. Higher EtOH concentrations cause upper critical solution temperature (UCST) behavior in the poly(N-isopropylacrylamide) (pNIPAAm) gel networks, which can induce an amplifying effect during bilayer bending. External ionoprints reliably and repeatedly invert the gel bilayer bending axis between water and EtOH. Placing the ionoprint at the gel/gel interface can lead to opposite shape conformations, but with no clear trend in the bending behavior. We hypothesize that this is due to the ionoprint passing through the neutral axis of the bilayer during shrinking in hot water. Finally, we demonstrate the ability of the actuators to achieve shapes unique to the specific external conditions towards developing more responsive and adaptive soft actuator devices. Full article

The delivery of drug molecules to tumor hypoxic areas could yield optimal therapeutic outcomes. This suggests that effective cancer-fighting micro- or nanorobots would require more integrated functionalities than just the development of directional propelling constructs which have so far been the main general emphasis in medical micro- and nanorobotic research. Development of artificial agents that would be most effective in targeting hypoxic regions may prove to be a very challenging task considering present technological constraints. Self-propelled, sensory-based and directionally-controlled agents in the form of Magnetotactic Bacteria (MTB) of the MC-1 strain have been investigated as effective therapeutic nanorobots in cancer therapy. Following computer-based magnetotactic guidance to reach the tumor area, the microaerophilic response of drug-loaded MC-1 cells could be exploited in the tumoral interstitial fluid microenvironments. Accordingly, their swimming paths would be guided by a decreasing oxygen concentration towards the hypoxic regions. However, the implementation of such a targeting strategy calls for a method to switch from a computer-assisted magnetotactic displacement control to an autonomous aerotactic displacement control. In this way, the MC-1 cells will navigate to tumoral regions and, once there, target hypoxic areas through their microaerophilic behavior. Here we show not only how the magnitude of the magnetic field can be used for this purpose but how the findings could help determine the specifications of a future compatible interventional platform within known technological and medical constraints. Full article

This paper presents a microfluidic device with electroplated vertical electrodes in the side walls for impedance measurement. Based on the proposed device, the impedance of NaCl solutions with different concentrations and polystyrene microspheres with different sizes was measured and analyzed. The electroplating and SU-8-PDMS (SU-8-poly(dimethylsiloxane)) bonding technologies were firstly integrated for the fabrication of the proposed microfluidic device, resulting in a tightly three-dimensional structure for practical application. The magnitude of impedance of the tested solutions in the frequency range of 1 Hz to 100 kHz was analyzed by the Zennium electrochemical workstation. The results show that the newly designed microfluidic device has potential for impedance analysis with the advantages of ease of fabrication and the integration of 3D electrodes in the side walls. The newly designed impedance sensor can distinguish different concentrations of polystyrene microspheres and may have potential for cell counting in biological areas. By integrating with other techniques such as dielectrophoresis (DEP) and biological recognition technology, the proposed device may have potential for the assay to identify foodborne pathogen bacteria. Full article

Wafer-level packaging (WLP) is a next-generation semiconductor packaging technology that is important for realizing high-performance and ultra-thin semiconductor devices. However, the molding process, which is a part of the WLP process, has various problems such as a high defect rate and low predictability. Among the various defect factors, the die shift primarily determines the quality of the final product; therefore, predicting the die shift is necessary to achieve high-yield production in WLP. In this study, the die shift caused by the flow drag force of the epoxy molding compound (EMC) is evaluated from the die shift of a debonded molding wafer. Experimental and analytical methods were employed to evaluate the die shift occurring during each stage of the molding process and that resulting from the geometrical changes after the debonding process. The die shift caused by the EMC flow drag force is evaluated from the data on die movements due to thermal contraction/expansion and warpage. The relationship between the die shift and variation in the die gap is determined through regression analysis in order to predict the die shift due to the flow drag force. The results can be used for die realignment by predicting and compensating for the die shift. Full article

Extreme point-of-care (POC) testing for infections, as performed (endured) in low-resource settings, developing countries, tropical areas, or in conditions following emergency crises or natural disasters, must be undertaken under environmental, logistic, and societal conditions which impose a significant deal of stress on local human populations and healthcare providers. For disease diagnostics or management, simple and robust biomedical equipment and reagents are required and needed. This chapter aims to overview some of these stresses (requirements) and intends to describe some of the solutions already engineered at the heart of centripetal (centrifugal) microfluidic platforms such as that of GenePOC Inc. to enable rapid, robust, and reproducible nucleic acid-based diagnostics of infectious diseases, to better control the morbidity and mortality of infections and the expanding threat posed by antimicrobial resistance. Full article

This paper presents a planar biochip consisting of electromagnetically coupled, symmetric, square open loops for the multiparameter microwave characterization of deionized water, a phosphate-buffered saline solution, and a fructose-deionized water solution. The characterization additionally includes the probing of an ultralow glucose concentration in a very small volume of human sera and in solutions of d-glucose powder and deionized water. The interaction between the coupled electromagnetic field and the aqueous solution sample translates into a predictable relationship between the electrical characteristics of the biochip (magnitude and phase of S-parameters, attenuation, phase constant, group delay, characteristic impedance, and effective complex permittivity) and the physical properties of the solution. Owing to the microfabrication technology used for fabricating the proposed microbiochip, it is possible to develop robust, compact square open loops with a microsized coupling gap that characterizes a very small volume (1 μL) of the sample. Additionally, the biochip’s impedance peaks at its resonances were modeled using glucose-level-dependent coupling capacitance between folded square open loops and mutual inductance between center-loaded T-shaped stubs. These peaks linearly shifted in frequencies and markedly varied in impedance. Consequently, a physiologically relevant amount of glucose (50–400 mg/dL) with a high sensitivity (up to 2.036 Ω/(mg·dL⁻¹)) and an ultralow detection limit (up to 4.8 nmol/L) was linearly detected. Full article