Fabrication and testing of microfluidic devices for blood cell separation

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.Blood separation is a strategic preliminary step in preparation to on-chip biological analysis. Two microfluidic devices for on-chip blood separation are presented. Both devices will be integrated to form the separation module of a Lab on Chip for non-invasive prenatal diagnosis. In the first device, a blood plasma separator, the separation of blood cells from plasma is made possible in microchannels by bio-physical effects such as an axial migration effect and Zweifach-Fung bifurcation law. Behaviour of mussel and human blood suspensions were studied alongside the effect of different geometries. The second device aims to separate fetal nucleated red blood cells based on their magnetic susceptibility. Biocompatible materials are used in the manufacturing of both devices.The authors acknowledge the financial support of the Engineering and Physical Science Research Council (EPSRC) through the funding of the Grand Challenge Project ‘3DMintegration’, reference EP/C534212/1. This work has also been supported by the EPSRC through a Doctoral Training Account (DTA) and has been performed at the Microsystems Engineering Centre (MISEC), Heriot-Watt University, Edinburgh. We thank Tim Ryan and Phil Summersgill, Epigem Ltd. for the fabrication of the blood plasma chips. The fabrication work was carried out in the Fluence Microfluidics Application Centre supported by the DTI and the OneNE Regional Development Agency as part of the UK's MNT Network

Experimental investigation of open-ended microwave oven assisted encapsulation process

An open ended microwave oven is presented with improved uniform heating, heating rates and power conversion efficiency. This next generation oven produces more uniform EM fields in the evanescent region forming part of the heating area of the oven. These fields are vital for the rapid and uniform heating of various electromagnetically lossy materials. A fibre optic temperature sensor and an IR pyrometer are used to measure in situ and in real-time the temperature of the curing materials. An automatic computer controlled closed feedback loop measures the temperature in the curing material and drives the microwave components to obtain predetermined curing temperature cycles for efficient curing. Uniform curing of the lossy encapsulants is achieved with this oven with typical cure cycle of 270 seconds with a ramp rate of 1oC/s and a hold period of 2 minutes. Differential scanning calorimeter based measurement for the pulsed microwave based curing of the polymer dielectric indicates a ~ 100% degree of cure

Towards a design process for computer-aided biomimetics

Computer-Aided Biomimetics (CAB) tools aim to support the integration of relevant biological knowledge into biomimetic problem-solving processes. Specific steps of biomimetic processes that require support include the identification, selection and abstraction of relevant biological analogies. Existing CAB tools usually aim to support these steps by describing biological systems in terms of functions, although engineering functions do not map naturally to biological functions. Consequentially, the resulting static, functional view provides an incomplete understanding of biological processes, which are dynamic, cyclic and self-organizing. This paper proposes an alternative approach that revolves around the concept of trade-offs. The aim is to include the biological context, such as environmental characteristics, that may provide information crucial to the transfer of biological information to an engineering application. The proposed design process is exemplified by an illustrative case study

Progress Towards a Multi-Modal Capsule Endoscopy Device Featuring Microultrasound Imaging

Current clinical standards for endoscopy in the gastrointestinal (GI) tract combine high definition optics and ultrasound imaging to view the lumen superficially and through its thickness. However, these instruments are limited to the length of an endoscope and the only clinically available, autonomous devices able to travel the full length of the GI tract easily offer only video capsule endoscopy (VCE). Our work seeks to overcome this limitation with a device (“Sonopill”) for multimodal capsule endoscopy, providing optical and microultrasound (μUS) imaging and supporting sensors1. μUS transducers have been developed with multiple piezoelectric materials operating across a range of centre frequencies to study viability in the GI tract. Because of the combined constraints of μUS imaging and the low power / heat tolerance of autonomous devices, a hybrid approach has been taken to the transducer design, with separate transmit and receive arrays allowing multiple manufacturing approaches to maximise system efficiency. To explore these approaches fully, prototype devices have been developed with PVDF, high-frequency PZT and PMN-PT composites, and piezoelectric micromachined ultrasonic transducer arrays. Test capsules have been developed using 3D printing to investigate issues including power consumption, heat generation / dissipation, acoustic coupling, signal strength and capsule integrity. Because of the high functional density of the electronics in our proposed system, application specific integrated circuits (ASICs) have been developed to realise the ultrasound transmit and receive circuitry along with white-light and autofluorescence imaging with single-photon avalanche detectors (SPADs). The ultrasound ASIC has been developed and the SPAD electronics and optical subsystem have been validated experimentally. The functionality of various transducer materials has been examined as a function of frequency and ultrasound transducers have been developed to operate at centre frequencies in the range 15 - 50 MHz. Ex vivo testing of porcine tissue has been performed, generating images of interest to the clinical community, demonstrating the viability of the Sonopill concept

Particle separation by phase modulated surface acoustic waves

High efficiency isolation of cells or particles from a heterogeneous mixture is a critical processing step in lab-on-a-chip devices. Acoustic techniques offer contactless and label-free manipulation, preserve viability of biological cells, and provide versatility as the applied electrical signal can be adapted to various scenarios. Conventional acoustic separation methods use time-of-flight and achieve separation up to distances of quarter wavelength with limited separation power due to slow gradients in the force. The method proposed here allows separation by half of the wavelength and can be extended by repeating the modulation pattern and can ensure maximum force acting on the particles. In this work, we propose an optimised phase modulation scheme for particle separation in a surface acoustic wave microfluidic device. An expression for the acoustic radiation force arising from the interaction between acoustic waves in the fluid was derived. We demonstrated, for the first time, that the expression of the acoustic radiation force differs in surface acoustic wave and bulk devices, due to the presence of a geometric scaling factor. Two phase modulation schemes are investigated theoretically and experimentally. Theoretical findings were experimentally validated for different mixtures of polystyrene particles confirming that the method offers high selectivity. A Monte-Carlo simulation enabled us to assess performance in real situations, including the effects of particle size variation and non-uniform acoustic field on sorting efficiency and purity, validating the ability to separate particles with high purity and high resolution

A rapid technique for the direct metallization of PDMS substrates for flexible and stretchable electronics applications

Metallization of a polydimethylsiloxane (PDMS)-based substrate is a challenge due to the difficulties in forming crack-free polymer and metal features using standard deposition techniques. Frequently, additional adhesion layers, rigid substrates, multiple processing steps (lift-off and etching) and expensive metal sputtering techniques are required, to achieve such metal patterns. This work presents a novel and rapid technique for the direct metallization of PDMS substrates using photolithography and electroless copper plating. The method has the advantage of not requiring expensive vacuum processing or multiple metallization steps. Electroless copper layer is demonstrated to have a strong adhesion to PDMS substrate with a high conductivity of (3.6 ± 0.7) × 107 S/m, which is close to the bulk copper (5.9 × 107 S/m). The copper-plated PDMS substrate displays mechanical and electrical stability whilst undergoing stretching deformations up to 10% due to applied strain. A functional electronic circuit was fabricated as a demonstration of the mechanical integrity of the copper-plated PDMS after bending

Particle separation in surface acoustic wave microfluidic devices using reprogrammable, pseudo-standing waves

We report size and density/compressibility-based particle sorting using on-off quasi-standing waves based on the frequency difference between two ultrasonic transducers. The 13.3 MHz fundamental operating frequency of the surface acoustic wave microfluidic device allows the manipulation of particles on the micrometer scale. Experiments, validated by computational fluid dynamics, were carried out to demonstrate size-based sorting of 5–14.5 μm diameter polystyrene (PS) particles and density/compressibility-based sorting of 10 μm PS, iron-oxide, and poly(methyl methacrylate) particles, with densities ranging from 1.05 to 1.5 g/cm3. The method shows a sorting efficiency of >90% and a purity of >80% for particle separation of 10 μm and 14.5 μm, demonstrating better performance than similar sorting methods recently published (72%–83% efficiency). The sorting technique demonstrates high selectivity separation of particles, with the smallest particle ratio being 1.33, compared to 2.5 in previous work. Density/compressibility-based sorting of polystyrene and iron-oxide particles showed an efficiency of 97 ± 4% and a purity of 91 ± 5%. By varying the sign of the acoustic excitation signal, continuous batch acoustic sorting of target particles to a desired outlet was demonstrated with good sorting stability against variations of the inflow rates

Optimised co-electrodeposition of Fe-Ga alloys for maximum magnetostriction effect

AbstractThe article reports the electrochemical deposition and characterisation of a 600nm thick Fe–Ga alloy film plated on a 20μm thick copper cantilever. The co-electrodeposition process was optimised for the production of Fe–Ga in the ratio of 81% Fe to 19% Ga, which is known to maximize the magnetostriction (MS) effect. The foil was cut into 1mm wide and 5mm long cantilevers and the deflection was measured with DC co-planar magnetic field intensities ranging from 0 to 60kA/m. The maximum strain coefficient λ was measured to be 96ppm for a field strength range 58kA/m. The field strain plot over exhibits a typical second order magnetically induced strain curve, as seen in other magnetostrictive materials