Daniel Puiu Poenar

Microcoils for transport of magnetic beads

Integrated magnetic devices were fabricated, consisting of arrays of microcoils of a novel structure, embedded in a silicon substrate, with small conductors asymmetrically shaped and with ferromagnetic pillars made of a magnetic alloy (NiCoP) as magnetic cores. These structures generated large magnetic field gradients that very effectively attracted magnetic beads. By alternatively injecting currents in an array of such microcoils placed in a microfluidic chamber, magnetic beads were guided in different movement modes and step sizes in a continuous flow.

Design and fabrication of Poly(dimethylsiloxane) arrayed waveguide grating

We have designed, fabricated and characterized poly(dimethylsiloxane) (PDMS) arrayed waveguide grating (AWG) with four-channel output for operation in the visible light wavelength range. The PDMS AWG was realized based on the single-mode PDMS rib waveguide. The device was designed for 1 nm channel spacing with the wavelength ranging from 639 to 644 nm. The measured insertion loss is 11.4 dB at the peak transmission spectrum and the adjacent crosstalk is less than -16 dB. The AWG device occupies an area of 7.5 × 15 mm(2). PDMS AWG has the potential for integration with microfluidics in a monolithic PDMS lab-on-a-chip device for visible light spectroscopy applications.

Design and fabrication of Poly(dimethylsiloxane) single-mode rib waveguide

We have designed, fabricated and characterized poly(dimethylsiloxane) (PDMS) single-mode rib waveguides. PDMS was chosen specifically for the core and cladding. Combined with the soft lithography fabrication techniques, it enables an easy integration of microoptical components for lab-on-a-chip systems. The refractive index contrast, of 0.07% between the core and cladding for single-mode propagation was achieved by modifying the properties of the same base material. Alternatively, a higher refractive index contrast, of 1.18% was shown by using PDMS materials from two different manufacturers. The fabricated rib waveguides were characterized for mode profile characteristics and confirmed the excitation of the fundamental mode of the waveguide. The propagation loss of the single-mode rib waveguide was characterized using the cutback measurement method at a wavelength of 635 nm and found to be 0.48 dB/cm for of 0.07% and 0.20 dB/cm for of 1.18%. Y-branch splitter of PDMS single-mode rib waveguide was further demonstrated.

Frequency dependence on the accuracy of electrical impedance spectroscopy measurements in microfluidic devices

This communication presents the dependence on frequency of the accuracy of electrical impedance spectroscopy (EIS) measurements in microfluidic devices. For this study, a very simple microfluidic device was used, with a hydrophilic microfluidic channel in which two parallel electrodes were patterned. Glass was the preferred substrate material for the fabrication of this microfluidic device, mainly due to its excellent dielectric properties even at relatively high frequencies. The testing was performed in air, and with DI water, ethanol and solutions of silica beads suspended in ethanol. The results show that the accuracy of the measurement increases with the frequency. The variation of the average of standard deviation error was between 13% at 10 kHz and less than 1% at 100 MHz. This clearly indicates that a high frequency range must be considered for further studies using electrical impedance spectroscopy in microfluidic devices.

An integrated on-chip platform for negative enrichment of tumour cells.

The study of cancer cells in blood, popularly called circulating tumour cells (CTCs), has exceptional prospects for cancer risk assessment and analysis. Separation and enrichment of CTCs by size-based methods suffer from a well-known recovery/purity trade-off while methods targeting certain specific surface proteins can lead to risk of losing CTCs due to Epithelial to Mesenchymal Transition (EMT) and thus adversely affect the separation efficiency. A negative selection approach is thus preferred for tumour cell isolation as it does not depend on biomarker expression or defines their physical property as the separation criteria. In this work, we developed a microfluidic chip to isolate CTCs from whole blood samples without targeting any tumour specific antigen. This chip employs a two-stage cell separation: firstly, magnetophoresis depletes the white blood cells (WBCs) from a whole blood sample and is then followed by a micro-slit membrane that enables depleting the red blood cells (RBCs) and retaining only the tumour cells. By creating strong magnetic field gradients along with customized antibody complexes to target WBCs, we are able to remove >99.9% of WBCs from 1:1 diluted blood at a sample processing rate of 500μL/min. This approach achieves an average of >80% recovery of spiked tumour cells from 2mL of whole blood in a total assay processing time of 50min without multiple processing steps.

Low stress PECVD amorphous silicon carbide for MEMS applications

We present a characterization of PECVD (plasma-enhanced chemical vapour deposition) amorphous silicon carbide films for MEMS/BioMEMS applications. For this applications a high deposition rate and a controllable value of the residual stress is required. The influence of the main parameters is analyzed. Due to annealing effect, the temperature can decrease the compressive value of the stress. The RF frequency mode presents a major influence on residual stress: in low frequency mode a relatively high compressive stress is achieved due to ion bombardment and, as a result, densification of the layer achieved. The PECVD amorphous silicon carbide layers presents a low etching rate in alkaline solutions (around 13 A/min in KOH 30% at 80°C) while in HF 49% the layer is practically inert. Amorphous silicon carbide can be used as masking layer for dry etching in XeF2 reactors (etching rate of 7 A/min). Finally, applications of PECVD amorphous silicon carbide layers for MEMS/BioMEMS applications are presented.

Colour sensor for (bio)chemical/biological discrimination and detection

Abstract Life science is a field of dynamic development and can benefit from the usage of microelectronics in numerous applications. Various devices for separation of different (bio)chemical components from a mixture could be miniaturized in silicon, but they need detectors at their output to identify and characterize the separated elements. The colour sensor is such a detector, and it was preferred because other classical approaches typically used in chemistry or biology employ IR or UV-based analysis, for which it is more difficult to design, optimize and fabricate a silicon-based sensor. Unlike classical detection (using three different filters placed on separate detectors) the proposed device is based on an entirely different approach, using vertically stacked detectors within a single structure that can be fabricated using CMOS-compatible processing. The main requirements for the design of such a vertically stacked multi-junction structure are presented, together with details regarding the most critical processing steps and process parameter values obtained after simulation which were used in the manufacturing of the first version of the device, including some optical design aspects.

EVALUATION OF CURRENT-CARRYING WIRES FOR MANIPULATION OF MAGNETIC MICRO/NANOPARTICLES FOR BIOMEDICAL APPLICATIONS

In this study we present a set of guidelines for the design of current carrying micro-conductors/micro-coils (MCs) for magnetic nanoparticles manipulation in biomedical applications. Precise spatial manipulation requires steep magnetic field gradients and due to the consequences of scaling laws, these gradients should be maximized as the size of the particle reduces. Conventional planar coils have many construction and functional limitations, such as generating only small magnetic field gradients, Joule heating, and limited ability to move particles with high spatial resolution. On the other hand, micro-coils can provide a satisfactory solution to all these problems. The geometrical and structural parameters play significant roles in determining the ability to move guide and transport nanoparticles. Design guidelines were generated from a detailed theoretical treatment and finite element analysis (FEA). The spatial distributions of magnetic fields, field gradients and magnetic forces on particles were simulated using FEA for different geometrical/structural parameters and wire arrangements. An array of wires create a chain of magnetic potential wells that are controllable in terms of magnitude and direction and therefore can be used to control the motion and position of magnetic nano-particles by tuning the current through the array.

Design of MEMS devices with optical apertures for the detection of transparent biological cells

This paper provides a novel technique to detect transparent biological living cells trapped in a microfluidic MEMS device by optical diffraction. The device essentially consists of an optical aperture or an aperture array patterned in metal layer and a microfluidic chamber positioned above the center of the aperture. When the cells in the chamber are illuminated through the aperture, the far-field diffraction pattern can be recorded by a CCD camera or a photodetector array. This diffraction pattern uniquely corresponds to the sizes, positions, and intrinsic optical properties of the aperture, cells, and the microfluidic chamber materials, so any unknown but relevant parameter is able to be extrapolated when all other parameters are fixed or identified. This paper describes in detail the designs of various microfluidic chambers and apertures for this application, and the development of a complete set of software for the analysis of the cells’ optical properties. Compared with other currently available methods for the detection of transparent living cells, this method has the advantages of simple device structure, easy to manipulate, able to simultaneously detect several cells of different species, as well as providing accurate and sensitive results. Besides the detection of living cells, this technique can also be used to detect or characterize other transparent or low optical absorption particles, such as polymer spheres or insoluble droplets, inside an aqueous solution.

Novel microfluidic device for cell characterization by impedance spectroscopy

The paper presents a novel microfluidic device for identification and characterization of cells in suspensions using impedance spectroscopy. The device consists of two glass wafers: a bottom wafer comprising a microfluidic channel with two electrodes added for impedance measurement, and a top glass wafer in which inlets and outlets are realized. The fact that the device is glass-based provides a few key advantages: reduced influence from parasitic components during measurements (due to the good isolation properties of the substrate), optical transparency and hydrophilic surface of the microfluidic channel. The latter feature is especially important as it enables sample suction due to capillarity forces only. Thus, no external pumping is required and only a small volume sample suffices for the measurement. The fabrication process of this device consists of three major steps. First, via-holes and inlet/outlet holes are executed in the top glass wafer by wet etching in a 49% HF solution using a low stress amorphous silicon/silicon carbide/photoresist mask. Second, the microfluidic channel is etched into the bottom wafer and Ti/Pt electrodes are then patterned on top of it using a spray coating-based lithography. The last processing step is bonding together the top and bottom glass wafers by employing a very thin adhesive intermediate layer (SU8). This adhesive layer was applied selectively only on the bottom die, from a Teflon cylinder, using a contact imprinting method. Finally, fabricated devices were successfully tested using DI water, phosphate buffer saline (PBS), and various types of both dead cells and living cells resuspended in PBS. Clear differences between dead and live cells have been observed. The impedance measurements were carried out in the frequency range 5 kHz to 10 MHz. The measured magnitude and phase were studied using different types of cells in Dulbeccos Minimal Essential medium (DMEM). The obtained impedance spectra revealed the characteristic spectra signature for each type of cell.