Micro and Nanosystems - Volume 7, Issue 3, 2015

Circulating tumor cells (CTC) are rare cells, which are shed from a heterogeneous primary tumor into circulation. Although there is only one CTC for every one billion peripheral blood cells, these cells spread the cancer through metastasis to secondary sites. Isolating and analyzing CTCs are challenging tasks that potentially can be solved with advances in micro- and nanotechnologies. Analyzing the isolated CTCs help to understand their role in the spreading of cancer and ultimately lead to successful treatment of the disease.

Tensile tests have been carried out to determine the failure strain of red blood cells. However, difficulties in reproducibly arise due to problems controlling the hold position of the cells during the test, which raises questions about the reliability of experimental data. Here, we investigate the effects of the hold position of the red blood cell on strain field during tensile testing using numerical simulations. Tensile tests were simulated in three hold positions. The results show significant variations in the deformed geometry of the red blood cell during the tensile test, as well as variations in strain distribution. Of the hold patterns examined, with an applied strain of 0.8, the misaligned stretch increased the maximum of the first principal strain by 65–85% in comparison to the aligned stretch. Although it would be ideal to precisely control the hold position and reproducibility, in practice this is not straightforward, and hence the effects of variations in the hold position should be considered when interpreting experimental data.

Traditional grid-based numerical methods, such as finite volume method (FVM), are not suitable to simulate multiphase biofluids (such as blood) at the microscale level. Alternatively, meshfree Lagrangian methods can deal with two or more finely dispersed phases moving relatively to each other. The Moving Particle Semi-Implicit Method (MPS), used in this study, is a deterministic particle method based on a Lagrangian technique to simulate incompressible flows. The advantages of particle methods over traditional grid-based numerical methods have motivated several researchers to implement them into a wide range of studies in computational biomicrofluidics. The main aim of this paper is to evaluate the accuracy of the MPS method by comparing it with numerical simulations performed by an FVM. Hence, simulations of a Newtonian fluid flowing through a constriction were performed for both methods. For the MPS, a section of the channel of 30x11.5x11.5 μm was simulated using periodic boundary conditions. The obtained results have provided indications that, if the initial particle distance is sufficiently small, the MPS method can calculate accurately velocity profiles in the proposed channel.

The most common and used technique to produce microfluidic devices for biomedical applications is the soft-lithography. However, this is a high cost and time-consuming technique. Recently, manufacturers were able to produce milling tools smaller than 100 μm and consequently have promoted the ability of the micromilling machines to fabricate microfluidic devices capable of performing cell separation. In this work, we show the ability of a micromilling machine to manufacture microchannels down to 30 μm and also the ability of a microfluidic device to perform partial separation of red blood cells from plasma. Flow visualization and measurements were performed by using a high-speed video microscopy system. Advantages and limitations of the micromilling fabrication process are also presented.

In vitro experiments of blood flow are usually performed with blood analogue fluids due to ethical and practical considerations. The ideal analogue must match the rheology of blood in multiple scales. Ideally, the blood analogue fluid should be a suspension of transparent particles with similar properties to red blood cells. PDMS particles are an interesting candidate because they are transparent, have a low refractive index and can be produced through polymerization by heating. Here we present a study to produce PDMS microparticles, to be used in biomimetic fluids, by droplet microfluidics. A microfluidic flow focusing device was employed to produce the droplets. A polymeric fluid (PDMS) was squeezed by two counter-flowing water streams (with 2% of SDS). The flow rate of the disperse phase (Qdis) was 1 μl min-1 and that of the continuous phase (Qcont) 5 μl min-1. Both liquids were forced to flow through a narrow slit (25 μm x 100 μm) located downstream the channels where PDMS stream breaks into droplets. In these conditions, the device operated in the jetting regime, forming polydispersed droplets. Monodispersed microparticles were also obtained in the dripping regime. The droplets were then cured thermally to form microparticles. The process of droplet formation was filmed with a high-speed camera and the movies were analyzed to relate the flow pattern to particle size distribution.

Shockwaves are widely used in clinical practices with applications including orthopedics, traumatology and lithotripsy. Its use as a therapeutic agent has also gained attention following reports that shockwaves enhance neoangiogenesis and cell proliferation. However, shockwave-generating devices are large, and therefore not suitable for endoscopic and endovascular operations. As such, we attempted to develop a miniature shockwave-generating device using an optical fiber with a 1 mm diameter. The tip of an optical fiber was finely polished, finished with chemical agents, and coated with a titanium film by vacuum evaporation. A pulse laser was applied to the titanium film through the optical fiber, and a shockwave was induced by thermoelastic effects. Finally, the shockwave released from the tip of the fiber was visualised in a water tank with a shadowgraphic technique, and the pressure was measured. The results showed that the shockwave pressure varied depending on whether the fiber tip was polished and whether the film was cracked. In the polished fibers with less cracked films, the shockwave pressure reached 0.3 MPa when a laser with the power density of 80 GW/m2 was introduced. Given the same laser power density, the shockwave pressure decreased by approximately 40% when the fiber tip was not polished and when the film was more cracked. These results highlighted the importance of strict quality control of the surface texture and the metallic film of the optical fibers when generating strong shockwaves.

This paper presents deoxyribonucleic acid (DNA) detection in an optical system by utilizing a multilayer polydimethylsiloxane (PDMS) microfluidic chamber through ultraviolet (UV) absorption process. Nucleic acids have high absorption in the UV range between 240 to 275 nm, and this property adapts to this work since DNA induces a significant absorbance change specifically at 260 nm. The multilayer PDMS microfluidic was produced by a spin coat process on the SU-8 mold. An optical system was developed to measure the change in light intensity over 500 μs, and the absorbance of the DNA samples were derived. The optical transmission properties of various samples with different thicknesses of PDMS are also investigated under UV light illumination. This characterization is to prove that the multilayer PDMS microfluidic is suitable as the device for DNA detection since the thickness is less than 1000 μm and having a higher percentage of the optical transmission. In DNA detection, significant experimental results were achieved, with the absorbance coefficient averaged between 0.07 and 0.09 a.u.

The paper considers the use of low-energy composite ion beam radiation to change the superconducting properties of ultrathin (5 nm) films of niobium nitride. It was found that the effect of ion irradiation causes a reduction in the superconducting transition temperature and increasing the resistivity of the film in the normal state. We studied the electrical properties of the irradiated films with doses up to 12.6 d.p.a. (for Nitrogen) in the temperature range from 2 to 300 K. It is found that at a temperature of 4.2 K films irradiated with doses of 12.6 d.p.a. and above showed electric conductivity mechanism corresponding to typical insulators, and irradiated in a dose range 1.8-9 d.p.a. exhibited electrical conductivity mechanism corresponding to metals. We considered the possibility to use the technique of selective changes in the atomic composition under ion beam irradiation to create the resistive elements for cryogenic temperatures.

Piezoelectric micro-power generator (PMPG) converts mechanical vibration energy into electric energy from human body via piezoelectric effects. In cardiac pacemakers, the use of PMPG eliminates the need for a traditional lithium iodide battery replacement. This paper covers fabrication process development of PMPG that is able to harvest the human body mechanical vibration to be converted into usable electrical power in low frequency range (1-100) Hz. The PMPG device developed has 10 μm SU8 proof mass, 200nm Au /20 nm Cr interdigitated electrode, 1.5 μm functioning PZT layer and 200 nm Si3N4 on 10 μm Si substrate. The Fabricated PMPG vibrate at 61 Hz with power density of 0.29 W/cm3 and can supply 3.33AC voltage, 2.19V DC voltage to the final load. The PMPG is suitable to power most of small electronic devices including cardiac pacemaker at frequency below 100 Hz.

The purpose of the present study was to investigate the best suited solvent evaporation method for the development of sustained release Losartan Potassium microspheres using ethyl cellulose polymer. Usually microspheres were prepared by oil-in-water (O/W), water-in-oil-in-water (W/O/W), water-in-oil-in-oil (W/O/O) and oil-in-oil (O/O) solvent evaporation methods. Among these methods, O/W and W/O/W methods were failed to produce the microspheres. Microspheres produced by W/O/O method was less encapsulation efficiency and rapid burst release. From these methods, O/O solvent evaporation method was found best method for the preparation of microspheres. In case of O/O method, yield of microspheres and encapsulation efficiency was higher as compared to other methods. The release of drug in distilled water was sustained (56.64%) up to 12 hours. FT-IR analysis showed no interaction between drug – polymer. The morphology of evaluated microspheres on FE-SEM was found spherical with pores on the surface. In XRD analysis, the crystalline nature of pure Losartan was changed to amorphous in microspheres. From this study it was observed that, a highly water soluble Losartan potassium drug can be loaded in ethyl cellulose sustained release microspheres using O/O solvent evaporation method.