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In this paper, we present the manufacturing process of a polymer microfluidic device which is currently being used to investigate wetting properties of nanostructured microchannels replicated in hydrophobic thermoplastic materials like cyclo-olefin co-polymer (COC), polypropylene (PP) or polymethylmetacrylate (PMMA). These devices feature large structural dynamics (feature sizes between 200 μm and 200 nm). The mold insert necessary was fabricated using a combination of precision machining with single-point diamond turning (SPDT).
Nanoporous devices constitute emerging platforms for selective molecule separation and sensing, with great potential for high throughput and economy in manufacturing and operation. Acting as mass transfer diodes similar to a solid-state device based on electron conduction, conical pores are shown to have superior performance characteristics compared to traditional cylindrical pores. Such phenomena, however, remain to be exploited for molecular separation. Here we present performance results from silicon membranes created by a new synthesis technique based on interferometric lithography. This method creates millimeter sized planar arrays of uniformly tapered nanopores in silicon with pore diameter 100 nm or smaller, ideally-suited for integration into a multi-scale microfluidic processing system. Molecular transport properties of these devices are compared against state-of-the-art polycarbonate track etched (PCTE) membranes. Mass transfer rates of up to fifteen-fold greater than commercial sieve technology are obtained. Complementary results from molecular dynamics simulations on molecular transport are reported.
A novel field effect transistor, based on the Screen Grid Field Effect Transistor concept, is proposed with an integrated Coulter Counter pore for amplification of the sensing signal. 3D TCAD simulations are performed on the use of the Coulter Counter Field Effect Transistor (CCFET) to detect the Influenza A virus. The gate of the transistor is the pore through which the bioparticles pass. This passage causes a change in the electrostatic conditions of the gate and thus changes the source-drain current, similar to ISFET operation. The structure of the CC-FET is optimised for bio-sensing and multi-particle passage through the gate hole is simulated. TCAD
results show that the CC-FET is capable of multi-particle and particle size detection.
Ion channels reconstituted into lipid bilayer membranes can be used as a very sensitive and selective platform for high-throughput drug screening applications. In order to employ suspended lipid bilayer membranes for these experiments in form of a “lab-on-a-chip” configuration, a robust and affordable platform is required. In our study, we investigated the feasibility of hosting lipid bilayer membranes across micron-size apertures ranging from 5 μm – 50 μm in silicon. On these substrates, lipid bilayers were formed and characterized concerning their seal resistance, capacitance and breakdown voltage. Seal resistance values of up to 60 GΩ could be achieved repeatedly on these substrates.
Manipulation of bio-fluids in microchannels faces many challenges in the development of lab-on-a-chip devices. We propose magnetically actuated artificial cilia which can propel fluids in microchannels. These cilia are magnetic films which can be actuated by an external magnetic field, leading to an asymmetric motion like that of natural cilia. The coupling between different physical mechanisms (magnetostatics, solid mechanics and fluid dynamics) is numerically established. In this work we quantify the flow through a microfluidic channel as a function of its geometry for a characteristic set of dimensionless parameters.
We report the synthesis and surface modification of bio-friendly ZnO based colloids, which have been used for cancer cell detection providing significant advantages on quantum confinement effects, high emission brightness in UV to blue-violate range, non-toxicity and a unique dual color imaging feature. The ZnO nanoparticles were single crystal nanoparticles having spherical shape in size of 1-2 or 4-5 nm depending on the surface capping agents. All the colloidal solutions were stable for 30-45 days. The surface capping is a more effective technique in controlling the nanoparticle size, while dopants are effective in modifying the bandgap and optical properties. Unique dual colour images with blue colour in nucleus and turquoise colour in cytoplasm were obtained using either pure ZnO or Co doped ZnO colloids on human osteosarcoma (Mg-63) cells. The dual colour function is the combined effects of quantum confinement and the bio-compatible surface capping groups. The cytotoxicity study proved no cell proliferation by the nanoparticles up to the concentration of 1000 μg/mL, which is the highest concentration reported so far. Since a dosage of only 50-100μM is enough for the in vivo detection on rate, these ZnO colloids have high potential for use as the detection media for Lab-on-a-Chip devices.
Hafnium(IV) oxide (HfO2) has replaced silicon oxide as a gate dielectric material in leading edge CMOS technology, providing significant improvement in gate performance for field effect transistors (FETs). We are currently exploring this high-k dielectric for its use in nucleic acid-based FET biosensors. Due to its intrinsic negative charge, label-free detection of DNA can be achieved in the gate region of high-sensitivity FET devices. Previous work has shown that phosphates and phosphonates coordinate specifically onto metal oxide substrates including aluminum and titanium oxides. This property can therefore be exploited for direct immobilization of biomolecules such as nucleic acids. Our work demonstrates that 5’ phosphate-terminated single stranded DNA (ssDNA) can be directly immobilized onto HfO2 surfaces, without the need for additional chemical modification or crosslinking. Non-phosphorylated ssDNA does not form stable surface interactions with HfO2, indicating that immobilization is dependent upon the 5’ terminal phosphate. Further work has shown that surface immobilized ssDNA can be hybridized to complementary target DNA and that sequence-based hybridization specificity is preserved. These results suggest that the direct DNA-HfO2 immobilization strategy can enable nucleic acid-based biosensing assays on HfO2 terminated surfaces. This work will further enable high sensitivity electrical detection of biological targets utilizing transistor-based technologies.
Immunoassays are currently the main analytical technique for quantification of a wide range of analytes of clinical, medical, biotechnological, and environmental significance with high sensitivity and specificity. Miniaturization of immunoassays is achieved using microfluidics coupled with integrated optical detection of the antibody-antigen molecular recognition reaction using thin-film amorphous silicon (a-Si:H) photodiodes. The detection system used consists of an a-Si:H photodiode aligned with a polydimethylsiloxane (PDMS) microchannel. An enzymatic reaction taking place in the microchannel yields a product which is a light-absorbent molecule and hence can be optically detected by the integrated photodiode. Specific antigen-antibody reaction was detected and distinguished from the non-specific reaction.
Here we propose to detail an innovative FIB instrumental approach and processing methodologies we have developed for sub-10 nm nanopore fabrication. The main advantage of our method is first to allow direct fabrication of nanopores in relatively large quantities with an excellent reproducibility. Second our approach offers the possibility to further process or functionalize the vicinity of each pore on the same scale keeping the required deep sub-10 nm scale positioning and patterning accuracy.
We will summarise the optimisation efforts we have conducted aiming at fabricating thin (10-100 nm thick) and high quality dielectric films to be used as a template for the nanopore fabrication, and at performing efficient and controlled FIB nanoengraving of such a delicate media.
Finally, we will describe the method we have developed for integrating these “single nanopore devices” in electrophoresis experiments and our preliminary measurements.
In this paper, we present a compact lab-on-chip system suited for label-free DNA analysis. The system can be fabricated on a conventional microscope glass slide using thin-film and thick-film technologies. It integrates a heating chamber, an electrowetting-based droplet handling system and a hydrogenated amorphous silicon (a-Si:H) photosensor array for DNA detection. At this stage of research we have designed and tested the individual functional units. The heating chamber incorporates a thin metal film heater optimized for uniform temperature distribution on a 1cm2 area. A forward-biased a-Si:H p-i-n junction is used for temperature monitoring, achieving a linear temperature dependence with -3.3 mV/K sensitivity. The droplet-handling unit, relying on the electrowetting method, is designed to move the sample from the heating chamber to the sensor array. The unit includes a set of metal pads beneath a layer of PDMS that provides both the electric insulation of the electrodes and the hydrophobic surface needed by the electrowetting technique. The UV sensor array allows measuring the DNA absorbance variation at 254nm related to the hybridization between probe-molecules contained in the sample and reference target molecules immobilized on the sensor surface. A preliminary test to detect the hybridization between a 25-mer single-stranded oligonucleotides and denaturated pBR 322 4162-mer single-stranded oligonucleotides has been carried out successfully.
Incorporation of biophotonic components in artificial devices is an emerging trend in exploring biomimetic approaches for green technologies. In this study, highly efficient, nanoscaled light antenna structures from green photosynthetic bacteria, known as chlorosomes, comprised of bacteriochlorophyll-c pigment arrays that are stable in aqueous environments are studied in an electrochemical environment for their photoelectrogenic capacity. Biohybrid electrochemical cells containing chlorosomes coupled to the native bacterial photosynthetic apparatus have a higher dark charge storage density (at least 10-fold) than electrochemical cells with decoupled chlorosomes. Nevertheless, upon light stimulation, the charge storage density, also known as charge injection capacity, for both electrochemical systems increased the charge stored near the electrode. Decoupled chlorosome-based systems showed a light-intensity dose-dependent response reaching a maximum change of ˜300 nC/cm2 at near sunlight intensities (˜80-100mW/cm2). Chronoamperometric studies under light stimulation conditions confirmed the photo-induced effect. Current studies are focused on optimization of the electrode/chlorosome interfacial properties across various heterogeneous interfaces. Successful implementation of harvesting photo-energy using the chlorosome or its derivatives may lead to substantial innovations in current biophotonic technologies, such as biofuel cells and retinal prosthetics.
In spite of considerable efforts, flow control in micro-channels remains a challenge owing to the very small ratio of channel/supply-system volumes, as well as the induction of spurious flows by extremely small pressure or geometry changes. We present here a robust and complete system for flow control in complex microchannel network that both monitors and controls all the flow relevant parameters, that is to say flow rate and pressure.
Based on a dynamic control of reservoir pressures at the end of each channel and external thermal flow-sensors, all the parameters are measured with a precision down to 25 μBar and 2nL/min. Thanks to adaptative feed back control loop, the MAESFLO can control either the flow rate or the pressure with high stability over long period whatever the microsystem characteristics. Compared to classic pumps, a significant increase of stability has been reached as no mechanical parts are involved. Indeed the flow rate is pulse free and is stable down to 0.1% of the full scale. Besides, pressure control enables to achieve short response time (less than hundreds of millisec).
The MAESFLO is thus a unique system to control flow in complex network architecture and can be considered as an alternative to integrated micro-valves using only external equipments. Indeed, the MAESFLO can stop the flow to nearly zero in one or several branches of a complex microfluidic network while keeping other flows constant. Sequential manipulation of liquids in a definite part of a micro-device is thus possible without expensive and time consuming fabrication processes. It can be particularly useful when dealing with washing steps in the case of biological assay for example.
Controlling flow with short response time along with high precision is also a key issue in microfluidic. By combining pressure actuation with flowrate monitoring, short response time are achievable keeping a high precision flow rate. It can be particularly useful for droplet generation and size control, droplet on demand generation, long time living cell perfusion and drug injection…
In this work we will present the benefit to control and monitor both pressure and flow rate with the MAESFLO. A lot of information can be extracted from these simple parameters, as hydraulic resistance, monophasic and biphasic apparent viscosity, the volume and the position of a trapped air bubble and many more. The proof of concept of stop flow control will also be shown with experimental results stressing the advantages of the “virtual micro-valve”.
Miniaturized and highly sensitive bio-sensors are attractive in various applications, such as medicine or food safety. Photonic crystal (PhC) microcavities present multiple advantages for rapid and accurate label-free optical detection. But their principle of operation (i.e. observation of a peak in transmission) makes their integration in serial arrays difficult. We present in this paper a multi-channel sensor consisting of several resonant PhC microcavities coupled to the same waveguide. The transmission spectrum shows as many dips as there are cavities, and each of the microcavities can act as an independent sensor. Preliminary results show the fabrication and characterization of a double-channel structure with small defects used as a solvent sensor.
Dry film resist has been used in the fabrication of Masters in microfluidic devices for droplet generation. The minimum feature size in the resist was controlled by the type of mask (transparency or electron beam Cr mask), the resolution of the pattern in transparency masks (2400 or 5080 dpi) and thickness of resist in the range from 35 to 140 μm. The Master patterns formed in dry resist were replicated as a Ni shim and then hot embossed into Plexiglas 99524. These devices were used to generate water-in-oil droplets with a well defined dependence of diameter and frequency on flow parameters. The application of dry laminar resist and transparency masks has allowed the rapid fabrication of prototype devices.
Drop on demand inkjet printing is a potential method for depositing enzymes onto electrodes for sensor applications. This technology offers drop sizes in the region of picolitres and allows a production rate up to 200 mm/s. This enables not only a more rapid method of device prototyping but also a method for possible miniaturization of the sensors themselves. However, previous work  has indicated that inkjet printing may cause a drop in the retained activity of the enzyme.
Here we assess the criticality of this drop in activity and how it may have been influenced by changes to the protein structure during printing. The enzyme used is glucose oxidase and the test methods include; protein analysis, in the form of analytical ultra-centrifugation and circular dichroism, scanning electron microscopy, atomic force microscopy and phase contrast microscopy, to analyse the surface topology of the electrodes and contact angle analysis, to assess the degree of spreading and the interactions between the drops and the electrode surface.
With glucose oxidase there is no change in the conformation, structure or hydrodynamic radius of the protein after printing. The analysis of the electrode surface shows a relatively smooth surface that is made up of individual graphite flakes laid down by a screen printing method. When contact angle and spreading analysis is carried out it demonstrates reliability in the printing process as well as a drop in the sessile volume of the drop in conjunction with a growth in the base diameter of the drop as expected. It also demonstrates a fairly quick rate of evaporation of the drop. Upon the addition of surfactants to the solution the spreading is seen to be more extensive in relation to the surfactant concentration, although some initial reduction in experienced at low concentrations which may be due to the absorption into the carbon surface.
We propose a novel method for self-assembled packing of silica microsphere in micro-channel which can be potentially used for on-chip chromatography. Chromatography has been one of the most widely used techniques for the analysis and separation of the mixtures of biochemical compounds in research laboratories and industrial factories. Numerous chromatography techniques such as High-Performance Liquid Chromatography (HPLC), Thin Layer Chromatography (TLC) use absorbents (ex: silica, alumina, cellulose) as stationary phase material . Effective loading of absorbents in those techniques has been a huge challenge since it requires additional implementation of high-pressure pump system (for HPLC) or limits selective coating of absorbents on supporting plate (for TLC). In order for chromatography to be efficiently integrated with micro-fluidic Lab-on-a-chip devices, novel techniques for easy and simple packing of absorbents within micro channels should be developed.
Solvent-evaporation based 2-D crystallization technique  can enable mono-dispersed micro-particles to be self-assembled by capillary attractive forces. We apply this technique to assemble dense packing of silica microsphere and form ultra thin layers (2˜3 layers) within open microchannel. Open micro-channel has been constructed by conventional photolithography of SU8 photoresist. A small droplet (Volume: 0.1μL) of silica suspension (Diameter: 3μm, Solvent: DI Water, Concentration: 1.25wt%) has been placed in the defined inlet of micro channel. Capillary force within the open SU8 microchannel induces the flow of silica suspension in the channel. The packing of microsphere starts from the outlet side of the channel, where the thickness of solvent drastically decreases due to sudden increase of cross-sectional area of channel, and this packing propagates to the inlet side of the channel until solvent evaporates completely. As a result, a dense packing of silica microspheres are successfully assembled and a thin layer of silica microspheres are formed within open micro-channel.
We will present the characterization of silica packing with regard to various process parameters and also will include theoretical interpretation of this packing technique in more detail. We will also present our future approach to integrate our technique on-chip chromatography applications.
Anodic aluminum oxide (AAO) template was prepared by using anodizing voltage step-decreasing method after two-step oxide method. Based on AAO template, Fe nanowires arrays were electrochemically deposited. Fe nanowires were coated by chitosan. Fe nanowires/chitosan was synthesized by glutaraldehyde as cross-linking reagent. By crosslinking α-human chorionic gonadotropin (α-HCG), biological probes with Fe nanowires/chitosan/antibody were prepared. An easy operating, easy taking and rapid reacting magnetic detecting system was developed after optimizing the geometry parameters of detect coil. Different concentration samples with 1, 2 and 5 g(Fe)/L were detected. The results show that the sensitivity of system is 0.2 g(Fe)/L and can be improve better.
The strength of adhesion at the cell-substrate interface is an important parameter in the design of many prosthetic implant material surfaces, due to the desire to create and maintain a strong implant-tissue bond. This study focuses on the mechanical strength of the interface and the ease of cell removal from ceramic coatings using normal and shear forces, but also looks at cell proliferation rates on the same series of surfaces.
This systematic study of cell proliferation and adhesion has been carried out on a series of oxide coated Ti6Al4V based substrates with a range of surface morphologies and chemistries. Oxide coatings were formed using Plasma Electrolytic Oxidation (the PEO process).
Cells were seeded at a low concentration onto substrates and proliferation monitored for up to three weeks. The same cell concentrations were seeded on samples for adhesion testing. These were cultured for a few days to ensure well established adhesion of viable cells. The normal and shear strength of osteoblasts (bone cells) and chondrocytes (cartilage cells) adhered to these substrates was measured using accelerated negative buoyancy within an ultracentrifuge.
The variation in proliferation rates on, and adhesive strengths to, the range of coatings, is discussed and related to morphological and chemical differences in the coatings. A comparison is made between the normal and shear strengths of the cell-coating bonds and the differences between the behaviour of the two cell types discussed.
The hot embossing properties of Cyclic Olefin Copolymer (COC) have been examined as a function of comonomer content. Six standard grades of COC with varying norbornene content (61-82 wt%) were used in these experiments in order to provide a range of glass transition temperatures, Tg. All grades of COC exhibited sharp increases in embossed depth over a critical range of temperature. The transition temperature in embossed depth increased linearly with norbornene content for both 35 and 70 μm deep structures. At temperatures above this transition, the dimensions of the embossed patterns were essentially independent of COC grade, the applied pressure and duration of loading. Channels formed above the transition in a regime of viscous liquid flow were extremely smooth in morphology for all grades. The average surface roughness, Ra, measured at the base of the channels decreased sharply at the transition temperature, with a levelling off at higher temperatures. Grades of COC with higher norbornene content exhibited extensive micro-cracking during embossing at temperatures close to the transition temperature.
On the macroscale, a laboratory scientist uses a large number of tools such as flasks, crucibles, spatulas, filter funnels, test tube holders and grippers. If laboratory procedures are to be miniaturized within chips, micro and nanoscale analogs of these macroscopic tools could provide enhanced functionality. In this paper, I describe research efforts in our group aimed at engineering three dimensional, tetherless and lithographically patterned miniaturized structures for lab on a chip applications.