Low Volume Whole Blood Sensor Biology Essay


The main objective of this project is focused on the development of a low-volume whole-blood sensor that could revolutionise the uptake of cardiac point-of-care testing. Nano-structuring of novel fluidic biosensors is envisaged for the development of such sensors, with good signal detectability using micro-litre amounts of patient blood sample. The fluidics system must filter out blood cells, to prevent them adhering to the sensor, and distorting the result. Typical uses include monitoring of cardiac enzymes, e.g. Troponin I, to aid in the diagnosis of a cardiac attack, determine the severity, and monitor recovery afterwards.

In this PhD project, the main emphasis was given to grow vertically aligned CNTs in various patternes and integrate them into polymeric microfluidic channel. These CNT pillars can act as a micro-particle filtersinside fluidic channels. The process parameter of thermal CVD and microwave plasma CVD to grow CNT of different aspect ratios on silicon and quartz substrates has been achieved. The fluidic channel with integrated CNTs will then be sealed and characterised further.

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1.2.2. Microfluidic channel for micro-particle filtering and flow control:

Microfluidic channels were prepared using two different methods i) On silicon/glass using SU8 photoresists by maskless photo-lithography technique. ii) On polymeric substrate (PMMA) using hot embossing technique. There devices were then further characterised by measuring the fluid flow velocity inside the channels. CNTs were also integrated into these channels as discussed earlier for micro-particle filtration. Simulation and modelling of fluid flow through a range of suitable geometries, and comparison with real flow conditions, were undertaken at IIT, Bombay.

1.3. Literature Review on CNT growth

1.3.1 Catalyst pre-treatment

In the chemical vapor deposition method for the synthesis of CNTs, catalyst pretreatment plays very important role in the growth process. According to the reported literature summarised below, pretreatment of catalytic nanoparticles is important to effectively synthesize CNTs. A number of publications have been considered here which shows the importance of catalyst pre-treatment for CNT growth. Some of them are described as follows:

S. Hofmann et.al [1] shows that for Fe or Co catalyst, it is necessary to reduce the thickness to below 3 nm, to achieve a transition from bamboo-like nanofibres with less than 40μm diameter, to approximately 5 nm diameter MWCNTs, with between 2 to 5 walls. The latter MWCNTs grow more than 50 times faster, but the catalyst poisons much more quickly. Ni catalyst, however, did not show such a growth transition, unless pre-treated with ammonia - which implies that without ammonia pre-treatment Ni catalyst may well produce large nanofibres, rather than true MWCNTs.

M. Cantoro et al [2] also shows similar conclusions about the effects of reducing the Fe or Co catalyst thickness to less than 3 nm for approximately 5 nm MWCNT diameter. Chao Hsun Lin et al [3] compares MPCVD and ECR-CVD growth of CNTs from thin foils of Fe, Co, and Ni. The bombardment energy of nitrogen plasma is found to be higher than for hydrogen plasma, so that the nitrogen plasma tends to clean the catalyst front surface better during deposition, keeping it active for longer. However, the higher bombardment energy of the nitrogen plasma tends to promote agglomeration of larger catalyst islands, leading to growth of bamboo-like CNTs.

S. Wang et al. [4] found that ammonia pre-treatment on relatively thick (> approximately 80 nm) Fe catalyst films gives approximately 10 to 25 nm particle size . The particle diameter increased with pre-treatment time (10 mins. up to 30 mins.), as expected if island agglomeration is occurring. For a range of microwave powers between 200 - 600 W, for the ammonia pre-treatment, a distinct minimum in particle diameter (approximately15 nm) occurred between 400 - 500 W. Similarly, CNTs were grown for a range of microwave powers, with a distinct minimum in nanotube diameter of 4 nm, at 500W. It clearly is necessary to optimise the microwave power for both the pre-treatment and the CNT growth process.

Lastly, the paper by H. Sato et al, "Effect of catalyst oxidation on the growth of carbon nanotubes by thermal chemical vapour deposition" [5] demonstrates that heat treatment of Fe catalyst on Si, in air at 700°C, before CNT growth, completely oxidises the catalyst, breaking it into islands which then do not further agglomerate. It was found that a greater than 7 times increase in CNT growth rate was achieved by catalyst pre-oxidation - it is believed that the pre-treatment prevents the formation of a Fe silicide, which would inhibit catalysis.

1.3.2 CNT growth by TCVD

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CVD is one of the popular technique for producing CNTs. This technique uses a hydrocarbon in vapor form which is thermally decomposed in the presence of a metallic catalyst. It is also commonly known as thermal/catalytic CVD. Compared with other synthesis methods, CVD is a one of the simple and economic technique for synthesizing CNTs at low temperature and ambient pressure, at the cost of crystallinity. It is versatile in that it harnesses a variety of hydrocarbons in any state (solid, liquid, or gas), enables the use of various substrates, and allows CNT growth in a variety of forms, such as powder, thin or thick films, aligned or entangled, straight or coiled, or even a desired architecture of nanotubes at predefined sites on a patterned substrate. It also offers better control over growth parameters. In fact, CVD has been used for producing carbon filaments and fibers since 1959 [6]. Using the same technique, soon after the re-discovery of CNTs by Iijima, Endo et al. [7] reported CNT growth from pyrolysis of benzene at 1100°C, while José- Yacamán et al. [8] formed clear helical MWNTs at 700°C from acetylene. In both cases, Fe nanoparticles were used as the catalyst. Later, MWNTs were also grown from ethylene [9], methane [10] and many other hydrocarbons. SWNTs were first produced by Dai et al.[11]from disproportionation of CO at 1200°C, catalyzed by Mo particles. Later, SWNTs were also produced from benzene [12], acetylene [13], ethylene [14], and methane [15, 16] using various catalysts.

Fig. 1a shows a diagram of the setup used for CNT growth by CVD in its simplest form. The process involves passing a hydrocarbon vapor (typically for 15-60 minutes) through a tube furnace in which a catalyst material is present at sufficiently high temperature (600-1200°C) to decompose the hydrocarbon. CNTs grow over the catalyst and are collected, upon cooling the system to room temperature. In the case of a liquid hydrocarbon (benzene, alcohol, etc.), the liquid is heated in a flask and an inert gas purged through it to carry the vapor into the reaction furnace. The vaporisation of a solid hydrocarbon (camphor, naphthalene, etc.) can be conveniently achieved in another furnace at low temperature before the main, high-temperature reaction furnace shown in Fig. 1a.

Fig. 1(a) : Schematic diagram of a CVD setup. (b) Probable models for CNT growth[R].

The catalyst material may also be solid, liquid, or gas and can be placed inside the furnace or fed in from outside. Pyrolysis of the catalyst vapor at a suitable temperature liberates metal nanoparticles in situ (the process is known as the floating catalyst method). Alternatively, catalyst-plated substrates can be placed in the hot zone of the furnace to catalyze CNT growth. Catalytically decomposed carbon species of the hydrocarbon are assumed to dissolve in the metal nanoparticles and, after reaching supersaturation, precipitate out in the form of a fullerene dome extending into a carbon cylinder (like the inverted test tube shown in Fig. 1b) with no dangling bonds and, hence, minimum energy [17,18]. When the substrate-catalyst interaction is strong, a CNT grows up with the catalyst particle rooted at its base (known as the 'base growth model'). When the substrate-catalyst interaction is weak, the catalyst particle is lifted up by the growing CNT and continues to promote CNT growth at its tip (the 'tip growth model'). Formation of SWNTs or MWNTs is governed by the size of the catalyst particle. Broadly speaking, when the particle size is a few nanometers, SWNTs form, whereas particles a few tens of nanometers wide favour MWNT formation. The three main parameters for CNT growth in CVD are the hydrocarbon, catalyst, and growth temperature. General experience is that low-temperature CVD (600-900°C) yields MWNTs, whereas a higher temperature (900-1200°C) reaction favors SWNT growth, indicating that SWNTs have a higher energy of formation (presumably owing to their small diameters, which results in high curvature and high strain energy). This could explain why MWNTs are easier to grow from most hydrocarbons than SWNTs, which can only be grown from selected hydrocarbons (e.g. CO, CH4, etc., that have a reasonable stability in the temperature range of 900-1200°C).

Common efficient precursors of MWNTs (e.g. acetylene, benzene, etc.) are unstable at higher temperatures and lead to the deposition of large amounts of carbonaceous compounds other than CNTs. Transition metals (Fe, Co, Ni) are the most commonly used catalysts for CNT growth, since the phase diagram of carbon and these metals suggests finite solubility of carbon in these transition metals at high temperatures. This leads to the formation of CNTs under the growth mechanism outlined above. Solid organometallocenes (ferrocene, cobaltocene, nickelocene) are widely used as catalyst materials because they liberate metal particles in situ that efficiently catalyze CNT growth. The catalyst particle size has been found to dictate the tube diameter. Hence, metal nanoparticles of controlled size can be used to grow CNTs of controlled diameter [19]. Thin films of catalyst coated onto various substrates have also proved successful in achieving uniform CNT deposits [20]. In addition, the material, morphology, and textural properties of the substrate greatly affect the yield and quality of the resulting CNTs. Zeolite supports with catalysts in their nanopores have resulted in significantly higher yields of CNTs with a narrow diameter distribution [21]. Alumina materials are reported to be better catalyst supports than silica owing to their strong metal-support interaction, which allows high metal dispersion and, thus, a high density of catalytic sites [22]. Such interactions prevent metal species from aggregating and forming unwanted large clusters that lead to graphite particles or defective MWNTs. The key to obtaining high yields of pure CNTs is achieving hydrocarbon decomposition on catalyst sites alone and avoiding spontaneous pyrolysis. It is remarkable that transition metals have proven to be efficient catalysts not only in CVD but also in arc-discharge and laser methods. This indicates that these apparently different methods might have a common growth mechanism for CNTs, which is not yet clear. CNTs have been successfully synthesized using organometallic compounds (nickel phthalocyanine [23] and ferrocene [24]) as carbon-cum-catalyst precursors, though the as-grown CNTs were mostly metal encapsulated. The use of ethanol has drawn attention for synthesizing SWNTs at relatively low temperatures (approximately850°C) on Fe-Co impregnated zeolite supports and Mo-Co coated quartz substrates [25-27]. Recently, a tree product, camphor, has been used to produce high yields of high-purity MWNTs [28-30]. Because of the low catalyst requirement with camphor, as-grown MWNTs are the least contaminated with metal, while the oxygen atoms present in camphor help oxidize amorphous carbon in situ [31]. CVD is ideally suited to growing aligned CNTs on desired substrates for specific applications, which is not feasible by arc or laser methods. Li et al. [32] have grown dense MWNT arrays on Fe-impregnated mesoporous silica prepared by a sol-gel process, Terrones et al. [33] have produced CNTs on Co-coated quartz substrates via CVD of a triazene compound with nearly no byproducts, while Pan et al. [34] have reported the growth of aligned CNTs of more than 2 mm in length over mesoporous substrates from acetylene. Highly aligned nanotubes for electronics have been grown from acetylene [35] using a Co catalyst impregnated in alumina nanochannels at 650°C, while pillars of parallel CNTs have been grown from ethylene on Fe-patterned Si plates at 700°C for field emission applications [30]. Bearing in mind that pyrolysis of a xyleneferrocene mixture leads to the growth of vertical CNTs on quartz [36], Ajayan and coworkers have produced organized assemblies of CNTs on thermally oxidized Si wafers [37,38]. Since CVD is a well known and well established industrial process, CNT production is easy to scale up. MWNTs of controlled diameter are being produced in large quantities (approximately100 g/day) from acetylene using nanoporous materials as the catalyst support [39]. Wang et al. [40] have developed a nano-agglomerate fluidized-bed reactor (a quartz cylinder 1 m long and 0.25 m wide) in which the continuous decomposition of ethylene gas on an Fe/alumina catalyst at 700°C produces a few kilograms of MWNTs per hour with a reported purity of 70%. Dai's group has scaled up SWNT production from methane using a Fe-Mo bimetallic catalyst supported on a sol-gel derived alumina-silica multicomponent material [41]. However, Smalley's lab still leads the way in the mass production of SWNTs (approximately10 g/day) by the high pressure carbon monoxide (HiPco) technique [42]. In this method, a Fe pentacarbonyl catalyst liberates Fe particles in situ at high temperatures, while a high pressure of CO (approximately30 atm) enhances the carbon feedstock manifolds, which significantly speeds up the disproportionation of CO molecules into carbon atoms and accelerates SWNT growth. Apart from large-scale production, CVD also offers the possibility of growing single nanotubes for use as probe tips in atomic force microscopes (AFM) or as field emitters in electron microscopes. Hafner et al. [43] have grown single SWNTs and MWNTs (1-3 nm in diameter) rooted in the pores of Si tips suitable for AFM imaging. In another approach, single SWNTs are grown directly onto pyramids of Si cantilever-tip assemblies [44]. In this case, a SWNT grown on the Si surface (controlled by the catalyst density on the surface) protrudes from the apex of the pyramid. As-grown CNT tips are smaller than mechanically assembled nanotube tips by a factor of three and enable significantly improved resolution. CVD-produced CNTs have great promise for the fabrication of sophisticated instruments and nanodevices.

1.3.3 CNT growth by MPCVD

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At present, there are a limited number of references to single wall CNTs grown by MPCVD. W.L. Wang et al in the paper "Low temperature growth of single-walled carbon nanotubes: small diameters with narrow distribution" [45] , shows the successful growth of nanotubes with a diameter range of approximately 1.0 nm ± 0.23 nm compared with a typical average figure of approximately 1.6 nm for CNTs grown by thermal CVD. Bimetallic Fe-Mo nanoparticles were used as the catalyst, but on porous MgO powder, rather than a solid substrate, probably because of the intention to separate the CNTs from the surface, and purify them (by HCl acid) for further analysis in the HRTEM.

Thermal CVD is typically carried out at 800°C. However it was found that the diameter of SWCNTs grown by MPCVD could be reduced as temperature reduced, from 700°C down to 500°C. It was also found, from Raman data, that both the D band increased in intensity, and the RBM mode signal became weaker (and noisier), as the temperature decreased from 700°C to 500°C. Below 500°C, little SWCNT growth occurred, the films being mostly amorphous or nanocrystalline carbon, and nanofibres. Nevertheless, it is encouraging to know that smaller diameter SWCNTs are possible by MPCVD, in case it becomes a requirement to grow higher bandgap SWCNTs with a view to achieving shorter wavelength light output (assuming metallic contacts that align to the bandgap mid-points can be made for wider bandgap material).

In the next paper, "Role of thin Fe catalyst in the synthesis of double and single wall carbon nanotubes via microwave chemical vapour deposition" [46] by Y. Y. Wang et al, is interesting for a number of reasons; firstly, vertically aligned SW and DW CNT growth by MPCVD is demonstrated, and confirmed by Raman analysis. The RBMs show distinct measurable peaks, and the D band peaks are very much lower than the G band peaks, confirming good quality tube growth. These CNTs were grown in an ASTeX 1.5kW microwave CVD reactor, similar to the MPCVD source at Nanotechnology and Integrated Bio-Engineering Centre (NIBEC). A 180 nm SiO2 layer on the Si wafer substrate was used to prevent formation of an Fe silicide, which would inhibit catalyst action. Interestingly, rather than pre-treat with a plasma, the substrates were firstly annealed in vacuum for 10 mins. at approximately 850°C, to form nanoislands, as confirmed by AFM. The substrate was then introduced into the MPCVD chamber a short hydrogen burst was used to ignite the plasma, and the hydrogen pressure was maintained throughout the growth, while acetylene and ammonia was introduced. The ammonia was used to reactively etch amorphous carbon and graphite-like material which can form during deposition, and limit the formation of the desired CNTs.


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3.0 Introduction to microfluidics

3.1 Introduction

Microfluidics is the science of design, manufacturing and formulating of devices and processes that deal with nanolitres of fluid. These devices range with dimensions from millimeters down to micrometers. Therefore the manufacturing processes involved differ greatly from devices on the macroscale. The system behaviour is affected when the dimensions of the device become comparable to the particle size of the fluid passing through. Common fluids used in microfluidics include protein or antibody solutions, blood samples, buffer solutions and bacterial or cell suspensions. The use of microfluidic devices to conduct biomedical research has a number of significant advantages over other methods;

The amount of reagents needed to obtain a diagnosis is relatively small due to the small dimensions involved.

The fabrication methods used to construct microfluidic devices are relatively cheap and are easily mass produced.

The fabrication of highly complex lad-on-a-chip devices is achievable which allows for faster diagnosis and removes the need for laboratory analysis.

Microfluidics fluid flow is based on a classical area of fluid dynamics: low-Reynolds-number flows. Flow in a microfluidic channel is described as having a low Reynolds number <100.

The Reynolds number is dependant on viscosity, fluid density, relative length scale and average velocity. When the Reynolds number is low as it is in microfluidic systems the turbulence is minimal. This means that the flow happens in a relatively predictable manner. The fluid moves through a microfluidic system using capillary forces. It occurs when the adhesive molecular forces are stronger than the cohesive intermolecular forces present in the fluid. However this may be an oversimplified model.The appearance of smaller and smaller devices has introduced many different variables such as;

Surface tension which itself is affected by surface roughness, electrical effects and van der Waals forces.

Complicated 3D patterning of the surface of the device

The presence of suspended particles which are comparable in size to the dimensions of the device.

The challenge of developing a device such as these is to utilise and understand these complex variables and manipulate them to one's advantage. On the device which will be developed, the fluid will be driven through the system by two different forces. Gravity will force the drop to enter the capillary channel at one end and then capillary action will draw the fluid through the system.

3.2 Literature Review on Microfluidics

3.2.1 General Microfluidic Theory

J. Lammertyn et al, [1] shows the development of a convection-diffusion-reaction model to simulate the behaviour of a flow inject analysis biosensor with respect to flow rate, fluidic channel dimensions, flow cell geometry, volume of substrate and the fluid used. This paper looks at the fluid flow using Navier-Stokes equations and Michaelis-Menten kinetics. A velocity flow profile was obtained and pressure driven fluidics and standard flow was compared. It was found that this modelling approach has a high potential in the design and development of high accuracy biosensors, regardless of the enzyme chosen.

B. Kuswandi et al [2] deals with the application of optical sensing systems in microfluidic devices. It is a review of the optical sensing approach for microfluidic devices, both the off chip approach (macroscale optical infrastructure coupled externally to the device) and on chip approach (which comprises the integration of micro optical functions into the microfluidic device. It was found that sensor size and shape profoundly affect the detection limits due to analyte transport limitation. The review concludes with an assessment of future directions of on chip integrated optical sensing microfluidic devices. I included this paper as it gives an overview of a different use of microfluidics and helps show how relevant these devices will be in medicine in the future.

P. Gould et al [3] discussed the potential, commercially, of microfluidic devices. Microfluidic lab-on-a-chip devices can contain everything needed to probe the tiniest of liquid samples and make a diagnosis. Microfluidic devices can be active (requiring external control) or passive (completely self contained devices). These items are single use devices designed to be discarded after one use. They then need to be cheap and easy to manufacture. This paper details the etching and lithography techniques that can be used to create a device. It talks about devices which can be designed with electronic devices impeded that manipulate an electric field and can move and process nanolitres samples through capillary circuitry. It also discusses the area of nanofluidics, using dimensions comparable to the size of the molecules in questions these molecules can be manipulated and squeezed then using key parameters such as light at certain wavelengths and this can be used to distinguish between different molecular types. The important factor as this paper states is moving these devices from the experimental and technical area into the commercial arena and turning it into a successful product.

P. Woias et al [4] explained previous 30yrs of microfluidic advancement and where it will head in the future. Starting in the 1970s a steadily growing and astonishing diversity of novel ideas and approaches to fabrication technology and applications have been coming to the fore in the development of MEMS devices. It deals specifically with the micropumps area of microfluidics and discusses the potential applications for this area in the future such as biochemical sensing. Microfluidics advancement will continue to fuel the development of micropump systems in the future. I reviewed this paper as it gives an overview of the history and progress of micropumps which is closely entwined with microfluidics and helps illustrate the vastness of the research area.

H.A. Stone et al [5] gives a brief overview of the main areas of microfluidics and the physics and variables involved in creating such a device. Many microfluidic devices have been developed over the past several years and these systems are becoming more and more important to the biomedical and pharmaceutical industries, as well as other areas outside these two main research topics. The ability to implement patterning on the nanoscale, create a device in the lab-on-a-chip concept, control and enhance chemical reactions, develop mixing and separation processes will offer research opportunities in the future and will then lead onto commercial opportunities for the successful devices. It details the areas which still need to be researched further such as; molecular interactions, surface forces and fluid flow. Again this article is of interest to this report as it gives a brief overview of the workings and physics involved in a microfluidic device.

T. Gervais et al [6] investigated mass transport and surface reactions in microfluidic systems in this paper. It deals with analysis of diffusion and laminar flow convection when combined with surface reactions relevant to microchemical assays. Analytic solutions for the concentration fields are compared to predictions from 2D computer models which are commonly used to interpret these results. Particular emphasis was placed on the characterisation of transport in shallow microfluidic channels. Two key parameters relevant to on-board chip biochemical assays and microfluidic sensors were studied and compiled; capture fraction of the bulk analyte and the saturation time scale at the reactive surface. This paper is relevant because it looks at the standard modelling for microfluidic systems to see just how accurate it is in the area of a biosensor.

3.2.2 Production Techniques

A.Pepin et al [7] describes the fabrication of microfluidic devices for biomolecule separation using an array of well-defined nanostructures. Two types of pattern replication of the same device configuration are considered, based on different methods of processing. The 1st approach uses a tri-layer nanoimprint lithography process to pattern a SiO2 substrate on top of which is stuck a plastic cover plate. The 2nd method involved directly imprinting thermoplastic polymer pellets to form bulk plates that are then thermally bonded together. The fabricated devices were characterised by epifluorescence microscopy, using a fluorescein solution to track leaks and fluid penetration. The findings of the report are those nanofluidic devices are achievable and could be manufactured for mass production.

C-H Wu and C-H Chen [8] described a new method for manufacturing a microfluidic structure on a polymer substrate is investigated in this paper. It uses an optical disc (CD) process to prevent damage to the mirror plate of the mould. The cycle time has also been reduced in comparison to the conventional methods by means of a new cooling system. The moulding system is comprised of a stamper and a vacuum system to join the mould insert with the mould. The time to change the mould is therefore dramatically reduced. It reduces the time required from several hours to a few minutes. The experiments demonstrated that this method is suitable for mass production. This shows another method for creating a microfluidic structure on a substrate.

The first paper to deal with SU-8 as a substance to create a microfluidic device was by J.M. Ruano-López et al.[9] SU-8 is a photodefinable epoxy and in this paper it was used to integrate optical sensors and microfluidic structures. The chip consists of optical sensors, waveguides and sealed microfluidic channels patterned in SU-8 on a silicon substrate. It describes the SU-8 fabrication process which will be discussed in great detail later in this report. The microchannels were sealed by low temperature adhesive bonding of the SU8 patterned films at a wafer level. The fabrication process was found to be fast, reproducible, CMOS compatible and a simple way to develop a lab on a chip device. The fabrication process discussed is of great interest to this paper as it detail the SU-8 process carried out which, more than likely, will be the method used.

X Sun.et al [10] developed a new method for rapid prototyping of hard polymer microfluidic systems using solvent imprinting and bonding. A layer of SU-8 photoresist was patterned on glass as a template for solvent imprinting. Poly(methyl methacrylate)(PMMA) was exposed to acetonitrile and then had the SU-8 template pressed into the surface, which provided appropriately imprinted channels and a suitable surface for bonding. A PMMA cover plate was fabricated in a similar manner and bonded together at room temperature at appropriate pressure. The total fabrication time was 15mins and the SU-8 template could be used to created nearly 30 PMMA chips. The lengths and depths of channels were investigated to discover the repeatability. This new solvent imprinting and bonding approach significantly simplified the fabrication process for structures in polymers such as PMMA.

L.Yu, & F.E.H Tay et al [11] proposed an adhesive bonding technique at wafer level again using SU-8 as the structural material. The adhesive was imprinted onto one of the surfaces and the aim was to bond the two surfaces using a low temperature method. It used three main steps; Firstly the adhesive layer is deposited onto the bonding surface by contact imprinting onto the SU-8 photoresist. The wafers are then placed in contact and aligned. In the final step the bonding is performed between 100oC and 200oC at a pressure of 1000N in a vacuum. This process was successfully tested in the fabrication process of a dielectrophoretic device.

B. Bilenberg et al [12], investigates an adhesive bonding technique for wafer level sealing of SU-8 based lab-on-a-chip Microsystems. Microfluidic channels were created using a standard lithography process in SU-8 photoresist and sealed with a pyrex glass lid by means of an intermediate layer of PMMA. This bonding technique was compared with SU-8 bonding and it was found that the slow flow of SU-8 resist during the sealing process caused the channels to be filled with resist. The bonding strengths of both methods were tested and it was found that PMMA has a bonding strength of around 16MPA when bonded under a force of 2000N and a temperature of 120oC. This method is promising for the devices that will be developed in this thesis and the method used by this thesis will be investigated further in experiments carried out in the lab at NIBEC.

J.S. Liu et al [13] shows Fabrication of microchannels on PMMA substrates using novel microfabrication techniques are investigated in this paper. The image of microchannels is transferred from a silicon master plate using hot embossing methods. The silicon master is electrostatically bonded to a Pyrex glass wafer which improves the device yield from 20 per master to over 100. This paper is mainly concerned with soft lithography techniques. However this method will not be used in my PhD

D.P. Poenar et al [14] reports on the creation of a microfluidic device from glass substrates that will be used to characterise cells using impedance spectroscopy. The device is constructed from two glass wafers. The bottom wafer has microfluidic channels and electrodes while the upper wafer has inlets and outlets. The main focus of this paper was the fabrication of the device, firstly, successfully applying a through-wafer wet etch to pattern inlets and outlets on the lid wafer. Secondly, patterning electrodes in the microfluidic channel on the bottom wafer. Finally bonding was carried out using an intermediate bonding layer (paralyene C) which requires a low bonding temperature, short time period for bond to take effect and high bond strength.

3.3 Carbon Nanotube Integration

S.G.Wang et al [15], showed the synthesis of Multi-walled carbon nanotubes (MWNTs) in this paper on silicon substrate using nickel catalyst with thickness varied from 2nm to 30 nm using microwave plasma chemical vapour deposition. The characterisation results obtained from this work showed that the diameter of produced MWNTs decreased with thickness of the nickel catalyst layer. MWNTs of 8nm have been obtained using a nickel catalyst layer of 2nm.

R. Pcionek, D.M. Aslam and D. Tománek [16] investigates the variables involved in the synthesis of CNTs. Nanotubes with diameters ranging from 20nm to 400nm and densities ranging from 108-109cm-2, were produced on metal coated silicon by MPCVD. The shapes and sizes of the nanostructures depended on growth condition and pre or post treatment of the samples. Presence of nitrogen in the growth or pre-growth atmosphere increased the density and vertical growth rate of the nanotubes. The growth rate on Nickel is slower than the growth rate on Iron and finally an ultrasonic treatment of nanotubes in methanol is demonstrated.

J.Y Kim et al [17], discusses incorporating SWNTs into a poly(dimethylsiloxane) (PDMS) based microfluidic channel. An 80μm thick horseshoe shaped SWNT microblock which had been physically immobilised with glucose oxidase (GOx) and horseradish peroxidase (HRP) was fabricated using a PDMS mould. The fabricated SWNT microblock was incorporated into a microfluidic channel for the bioreaction on a microscale. This microfluidic device was tested for the spectroscopic glucose detection and the results showed that the glucose can be detected linearly in a wide range of concentrations. This shows the CNTs can be used in conjunction with a microfluidic device to create a biosensor.

G. Chen [18] focuses on recent advances in fabrication of electrochemical detectors in microchip and microfluidics using CNT in this review paper. The subject covered include CNT based electrochemical detectors in microchip capillary electrophoresis (CE), CNT based electrochemical detectors in conventional CE boron doped diamond electrochemical detectors in microchip CE and boron doped diamond electrochemical detectors in conventional CE. The properties found make CNTs and boron doped diamond promising materials in the areas of electrochemical detection in microfluidic analysis systems.

J. Xu et al [19], fabricate a carbon nanotube/polystyrene composite electrodes were as sensitive amperometric detectors of capillary electrophoresis (CE) for the determination of rutin and quercetin in Flos Sophorae Immaturus. The composite electrode was fabricated on the basis of in-situ polymerisation of a mixture of CNT and styrene in the microchannel of a piece of fused silica capillary under heat. The surface morphologies were investigated using a scanning electron microscope. The performance of this unique system has been demonstrated by separating and detecting rutin and quercetin. The system demonstrated long term stability, reproducibility and shows a lot of potential to be sued in a wide range of applications in microfluidic analysis and flow injection analysis.