This PDF file contains the front matter associated with SPIE Proceedings Volume 8251, including the Title Page, Copyright information, Table of Contents, and the Conference Committee listing.

Infectious diseases cause 10 million deaths each year worldwide, accounting for ~60% of all deaths of children aged 5- 14. Although these deaths arise primarily through pneumonia, TB, malaria and HIV, there are also the so called "neglected diseases" such as sleeping sickness and bilharzia, which have a devastating impact on rural communities, in sub-Sahara Africa. There, the demands for a successful Developing World diagnostic are particularly rigorous, requiring low cost instrumentation with low power consumption (there is often no fixed power infrastructure). In many cases, the levels of infection within individuals are also sufficiently low that instruments must show extraordinary sensitivity, with measurements being made in blood or saliva. In this talk, a description of these demands will be given, together with a review of some of the solutions that have been developed, which include using acoustics, optics and electrotechnologies, and their combinations to manipulate the fluid samples. In one example, we show how to find a single trypanosome, as the causative agent of sleeping sickness.

Cell-based testing is a key step in drug screening for cancer treatments. A microfluidic platform can permit more precise control of the cell culture microenvironment, such as gradients in soluble factors. These small-scale devices also permit tracking of low cell numbers. As a new screening paradigm, a microscale system for integrated cell culture and drug screening promises to provide a simple, scalable tool to apply standardized protocols used in cellular response assays. With the ability to dynamically control the microenvironment, we can create temporally varying drug profiles to mimic physiologically measured profiles. In addition, low levels of oxygen in cancerous tumors have been linked with drug resistance and decreased likelihood of successful treatment and patient survival. Our work also integrates a thin-film oxygen sensor with a microfluidic oxygen gradient generator which will in future allow us to create spatial oxygen gradients and study effects of hypoxia on cell response to drug treatment. In future, this technology promises to improve cell-based validation in the drug discovery process, decreasing the cost and increasing the speed in screening large numbers of compounds.

The early detection of changes in the level and composition of algae is essential for tracking water quality and environmental changes. Current approaches require the collection of a specimen which is later analyzed in a laboratory: this slow and expensive approach prevents the rapid identification of changes in algae species dynamics and hinders a quick response to potential outbreaks. In a recent work, we presented a microfluidic chip for classifying and quantifying algae species in water. Here, we study the device performance and specifically compare the difference in results obtained by using a discriminant analysis classification approach and a neural network pattern recognition approach. Using both of these methods, we demonstrate the classification of algae by species, of microspheres by size, and of a detritus/cyanobacteria mixture by type. In each of the demonstrations here, the neural network outperforms the discriminant analysis method.

The Nano Intravital Device, or NANIVID, is under development as an optically transparent, implantable tool to study the tumor microenvironment. Two etched glass substrates are sealed using a thin polymer membrane to create a reservoir with a single outlet. This reservoir is loaded with a hydrogel blend that contains growth factors or other chemicals to be delivered to the tumor microenvironment. When the device is implanted in the tumor, the hydrogel will swell and release these entrapped molecules, forming a gradient. Validation of the device has been performed in vitro using epidermal growth factor (EGF) and Mena_INV, a highly invasive, rat mammary adenocarcinoma cell line. In both 2-D and 3-D environments, cells migrated toward the gradient of EGF released from the device. The chorioallantoic membrane (CAM) of White Leghorn chicken eggs is being utilized to grow xenograft tumors that will be used for ex vivo cell collection. Device optimization is being performed for in vivo use as a tool to collect the invasive cell population. Preliminary cell collection experiments in vivo were performed using a mouse model of breast cancer. As a second application, the device is being explored as a delivery vehicle for chemicals that induce controlled changes in the tumor microenvironment. H₂O₂ was loaded in the device and generated intracellular reactive oxygen species (ROS) in cells near the device outlet. In the future, other induction targets will be explored, including hypoglycemia and the manipulation of extracellular matrix stiffness.

It is known that tumor-initiating cells with stem-like properties will form spherical colonies - termed mammospheres - when cultured in serum-free media on low-attachment substrates. Currently this assay is performed in commercially available 96-well trays with low-attachment surfaces. Here we report a novel microsystem that features on-chip mammosphere culture on low attachment surfaces. We have cultured mammospheres in this microsystem from well-studied human breast cancer cell lines. To enable the long-term culture of these unattached cells, we have integrated diffusion-based delivery columns that provide zero-convection delivery of reagents, such as fresh media, staining agents, or drugs. The multi-layer system consists of parallel cell-culture chambers on top of a low-attachment surface, connected vertically with a microfluidic reagent delivery layer. This design incorporates a reagent reservoir, which is necessary to reduce evaporation from the cell culture micro-chambers. The development of this microsystem will lead to the integration of mammosphere culture with other microfluidic functions, including circulating tumor cell recovery and high throughput drug screening. This will enable the cancer research community to achieve a much greater understanding of these tumor initiating cancer stem cells.

This study demonstrates improved kinetics for the formation of self-assembled monolayers (SAMs) of alkanethiols on gold nanoparticle substrates. A computational model was developed to predict SAM growth kinetics. Based on the predictions from the model, SAMs of 11-mercaptoundecanoic acid (11-MUA) and 1-octanethiol (1-OT) were formed by incubation of gold nanoparticle chips in an ethanolic 10 mM solution within 20 min. The performance of this novel rapid SAM formation protocol was compared with a conventional 24 hour incubation protocol. Binding capacity of the alkanethiol SAM was investigated for a 20 min incubation protocol using biotin-streptavidin. For this purpose, the SAM loaded gold nanoparticle chips were modified with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) to allow attachment of EZ-Link amine PEG3 biotin to the 11-MUA molecules. Binding reactions were monitored in real time using localized surface plasmon resonance (LSPR) spectroscopy. The resulting LSPR absorbance peak shift was comparable to the experimental results for biotin-streptavidin reported in literature. Results of this study suggest that formation of a high quality alkanethiol SAM within 20 min on gold nanoparticles surfaces is possible and could greatly reduce the time and cost compared to conventional 24 h incubation protocols.

There is a need to design an integrated microfluidic platform as simple and lean as possible in order to meet the requirements for a miniaturized system. Magnetic particles show a great versatility in performing several of the functions necessary in many microfluidic assays. We therefore have developed a compact portable system to perform magneticbead- based sample preparation steps in a chip such as DNA-extraction or particle-enhanced mixing of reagents. A central application in a standard biochemical/biological/medical laboratory is represented by PCR. The execution of a cyclic heating profile during PCR is a considerable stress for chip and liquid inside the chip because evaporation and uncontrolled condensation or unintended motion of the PCR solution. One strategy to overcome this problem consists of the implementation of valves flanking a stationary PCR in appropriate incubation cavities. In addition to the well-known elastomeric membrane valves, wax-valves mechanical turning or rotary valves flanking the PCR chamber, we present in this paper the use of clustered magnetic particles as blocking valves for such reaction chambers. We report on the capability of assembled magnetic particles to act as rather simple configurated valves during a PCR typical temperature regime. These novel valves efficiently withstand 1.5 bar pressure, prevent loss of aqueous liquid inside the reaction chamber via evaporation or bubble formation, and do not express adverse effects on any biological reaction inside the chip-based PCR cavity. The latter properties have been proven by a set of different PCRs performed in chip-based cavities.

We describe a microfluidic device for studying the orientational dynamics of microrods. The device enables us to experimentally investigate the tumbling of microrods immersed in the shear flow in a microfluidic channel with a depth of 400 μm and a width of 2.5 mm. The orientational dynamics was recorded using a 20X microscopic objective and a CCD camera. The microrods were produced by shearing microdroplets of photocurable epoxy resin. We show different examples of empirically observed tumbling. On the one hand we find that short stretches of the experimentally determined time series are well described by fits to solutions of Jeffery's approximate equation of motion [Jeffery, Proc. R. Soc. London. 102 (1922), 161-179]. On the other hand we find that the empirically observed trajectories drift between different solutions of Jeffery's equation. We discuss possible causes of this orbit drift.

Neural prostheses are technical systems that interface nerves to treat the symptoms of neurological diseases and to restore sensory of motor functions of the body. Success stories have been written with the cochlear implant to restore hearing, with spinal cord stimulators to treat chronic pain as well as urge incontinence, and with deep brain stimulators in patients suffering from Parkinson's disease. Highly complex neural implants for novel medical applications can be miniaturized either by means of precision mechanics technologies using known and established materials for electrodes, cables, and hermetic packages or by applying microsystems technologies. Examples for both approaches will be introduced and discussed. Electrode arrays for recording of electrocorticograms during presurgical epilepsy diagnosis have been manufactured using approved materials and a marking laser to achieve an integration density that is adequate in the context of brain machine interfaces, e.g. on the motor cortex. Microtechnologies have to be used for further miniaturization to develop polymer-based flexible and light weighted electrode arrays to interface the peripheral and central nervous system. Polyimide as substrate and insulation material will be discussed as well as several application examples for nerve interfaces like cuffs, filament like electrodes and large arrays for subdural implantation.

We present an integrated flexible probe for deep brain optical stimulation and electrical recording, termed as "Optitrode". This device features an annular light guide consisting of layered transparent polymer and silica, and is fabricated by a unique process we developed: V-groove guided capillary assembly (VGCA), by which a single or multiple microwires can be integrated inside the light guide with high precision. The Optitrode design promises an ultrahigh length-to-diameter ratio > 500 (5 cm long, < 100 μm diameter), enabling minimally-invasive deep brain applications. Furthermore, the highly flexible nature of Optitrode could address a current barrier in rigid brain implants with limited life-time by conforming to the brain micromotion during long-term operation.

Recent advances in MEMS technology have provided an opportunity to develop microfluidic devices with enormous potential for portable, point-of-care, low-cost medical diagnostic tools. Hand-held flow cytometers will soon be used in disease diagnosis and monitoring. Despite much interest in miniaturizing commercially available cytometers, they remain costly, bulky, and require expert operation. In this article, we report progress on the development of a battery-powered handheld blood analyzer that will quickly and automatically process a drop of whole human blood by real-time, on-chip magnetic separation of white blood cells (WBCs), fluorescence analysis of labeled WBC subsets, and counting a reproducible fraction of the red blood cells (RBCs) by light scattering. The whole blood (WB) analyzer is composed of a micro-mixer, a special branching/separation system, an optical detection system, and electronic readout circuitry. A droplet of un-processed blood is mixed with the reagents, i.e. magnetic beads and fluorescent stain in the micro-mixer. Valve-less sorting is achieved by magnetic deflection of magnetic microparticle-labeled WBC. LED excitation in combination with an avalanche photodiode (APD) detection system is used for counting fluorescent WBC subsets using several colors of immune-Qdots, while counting a reproducible fraction of red blood cells (RBC) is performed using a laser light scatting measurement with a photodiode. Optimized branching/channel width is achieved using Comsol Multi-Physics™ simulation. To accommodate full portability, all required power supplies (40v, ±10V, and +3V) are provided via step-up voltage converters from one battery. A simple onboard lock-in amplifier is used to increase the sensitivity/resolution of the pulse counting circuitry.

For complex biological or diagnostic assays, the development of an integrated microfluidic device can be difficult and error-prone. For this reason, a modular approach, using individual microfluidic functional modules for the different process steps, can be advantageous. However often the interconnection of the modules proves to be tedious and the peripheral instrumentation to drive the various modules is cumbersome and of large size. For this reason, we have developed an integrated instrument platform which has generic functionalities such as valves and pumps, heating zones for continuous-flow PCR, moveable magnets for bead-based assays and an optical detection unit build into the instrument. The instrument holds a titerplate-sized carrier in which up to four microscopy-slide sized microfluidic modules can be clipped in. This allows for developing and optimizing individual assay steps without the need to modify the instrument or generate a completely new microfluidic cartridge. As a proof-of-concept, the automated sample processing of liquor or blood culture in microfluidic structures for detection of currently occuring Neisseria meningitidis strains was carried out. This assay involves the extraction of bacterial DNA, the fluorescent labeling, amplification using PCR as well as the hybridization of the DNA molecules in three-dimensional capture sites spotted into a microchannel. To define the assay sensitivity, chip modules were tested with bacteria spiked samples of different origins and results were controlled by conventional techniques. For liquor or blood culture, the presence of 200 bacteria was detected within 1 hour.

In recent years there has been an increasing demand for functional integration in microfluidic devices. This integration often requires the use of different materials in order to generate the demanded performance. Typical examples for such integrated functionalities are on-chip valves or areas used for sealing one component against another, e.g. a microfluidic manifold against a sensor chip. Such functionalities have been described in the literature mainly by using elastomeric materials such as PDMS. However this material suffers from the lack of suitable high-volume manufacturing processes and its high material cost. For production of such hybrid material devices, two-component injection molding can prove to be a suitable microfabrication method. In our paper we will present several examples for such two-component injection molded microfluidic components such as a mechanical turning valve, microfluidic chips with gasketing structures and chips with plug seals to close a fluidic port.

Electrodes are necessary components for measuring changes in electrical properties in many microfluidic devices. The consistency of the dimensions of manufactured electrode is critical to the repeatability of measurements. We analyze the electrode dimensions to characterize a manufacturing process. Optical imaging is used to obtain high-resolution images of the electrodes and an algorithm was developed in order to estimate the critical dimensions of interdigitated electrode fingers from the images. The results show that the dimensional variation inherent in the manufacturing of the electrodes had insignificant effect on the performance of the electrodes.

Disposable microfluidic systems are used to avoid sample contamination in a variety of medical and environmental monitoring applications. A contactless hot intrusion (HI) process for fabricating reusable polymer micromolds with near "optical quality" surface finishes is described in this paper. A metallic hot intrusion mask with the desired microchannels and related passive components is first machined using a tightly focused beam from a diode-pumped solid-state (DPSS) laser. The polymer mold master is then created by pressing the 2D metallic mask onto a polymethylmethacrylate (PMMA) substrate. Since it is a contactless fabrication process the resultant 3D micro-reliefs have near optical quality surface finishes. Unfortunately, the desired micro-relief dimensions (height and width) are not easily related to the hot intrusion process parameters of pressure, temperature, and time exposure profile. A finite element model is introduced to assist the manufacturing engineer in predicting the behavior of the PMMA substrate material as it deforms under heat and pressure during micromold manufacture. The FEM model assumes that thermo-plastics like PMMA become "rubber like" when heated to a temperature slightly above the glass transition temperature. By controlling the material temperature and maintaining its malleable state, it is possible to use the stress-strain relationship to predict the profile dimensions of the imprinted microfeature. Examples of curved microchannels fabricated using PMMA mold masters are presented to illustrate the proposed methodology and verify the finite element model. In addition, the non-contact formation of the micro-reliefs simplifies the demolding process and helps to preserve the high quality surface finishes.

Components for on-chip storage and delivery of liquid reagent are necessary for many commercial applications of lab-on- a-chip technology. One such system uses a 'blister-pack' that is pushed by an actuator. This paper explores the sensitivity of the flow rate produced by a blister-actuator pair to the expected manufacturing variations in its dimensions. A numerical model of the blister-actuator pair is developed and the tool of Variation Simulation Modeling (VSM) is used to determine the robustness of fluid delivery. For a flow-rate requirement of +/- 10%, the number of out-of-spec parts is found to be less than 0.01%. The critical dimensions that need to be controlled to improve robustness are also identified.

In this paper, we present a system for fluorescent monitoring of multiple gas concentrations using a simple and robust single detector setup. Two gas-sensitive fluorescent films are illuminated by two separate excitation sources modulated at different frequencies. Cross-polarization is used to shield the excitation light from the detector, allowing fluorescent signals from both films to be simultaneously monitored and quantified using a microprocessor and lock-in detection. Simultaneous detection of O₂ and CO₂ in a mixture of gases is done as a proof-of-concept of this frequency discrimination technique. The detection of oxygen is based on the fluorescence quenching of platinum octaethylporphine (PtOEP) lumiphore in presence of O₂. The detection of CO₂ is based on fluorescence quenching of hydroxypyrene trisulfonic acid trisodium salt (HPTS) in presence of CO₂. A single microprocessor is used to drive the excitation source (different color LEDs), and sample and analyze the detector response at the two different frequencies. The device demonstrated minimal crosstalk between the O₂ and CO₂ signals. The O₂ concentration was measured in the useful range between 20 and 0%, and CO₂ demonstrated a useful range between 5% and 0%. The polarization filtering is color-independent and can be readily extended to systems with more than two colors; due to the frequency discrimination, it is immune to cross-talk in which one dye excites another. The whole arrangement is a compact, lowcost, simultaneous multi-color fluorescent sensor system suitable for many biological, chemical, and gas-monitoring applications.

This work reports on continuing development of a lab-on-a-chip sensor for electrochemical detection of heavy metal zinc in blood serum. The sensor consists of a three electrode system, including an environmentally-friendly bismuth working electrode, a Ag/AgCl reference electrode, and a gold auxiliary electrode. By optimizing the electrodeposition of bismuth film, better control of fabrication steps and improving interface between the sensor and potentiostat, repeatability and sensitivity of the lab-on-a-chip sensor has been improved. Through optimization of electrolyte and stripping voltammetry parameters, limits of detection were greatly improved. The optimized sensor was able to measure zinc in in the physiological range of 65-95 μg/dL. Ultimately, with further development and integrated sample preparation sensor system will permit rapid (min) measurements of zinc from a sub-mL sample (a few drops of blood) for bedside monitoring.

A digital microfluidic architecture is introduced for micron-scale localized fluid actuation and in in-situ optical sensing. Contemporary device integration challenges related to localization and device scalability are overcome through the introduction of a bi-layered digital microfluidic multiplexer. Trinary inputs are applied through differential combinations of voltage signals between upper (column) electrodes and lower (row) electrodes. The ultimate layout provides increased scalability for massively parallel microfluidic actuation applications with a minimal number of inputs. The on-chip sensing technique employed here incorporates a microlens in a folded-cavity arrangement (fabricated by a new voltage-tuned polymer electro-dispensing technique). Such a geometry heightens the sensitivity between the optical probe and fluid refractive properties and allows the device to probe the refractive index of the internal fluid. This optical refractometry sensing technique is merged with the actuation capabilities of the digital microfluidic multiplexer on a single lab-on-a-chip device.

A recent advancement in the study of drug development for cardiovascular diseases is based on measuring the mechanical response of a single cardiomyocyte to various drug concentrations. This method requires delivering a specific dose of the drug over a short period of time while measuring the forces exerted by a cell that is kept inside a microchamber. However, the exact drug dosage is difficult to control for rapid variations in drug concentration, which hinders the accuracy of the measurements. This paper reports a highly sensitive technique for accurate and real-time measurement of minute variations in drug concentration. The fluid electrical conductivity is monitored using an array of electrodes along a micro-channel that eventually leads to the microchamber where the cardiomyocyte is placed. The microfluidic setup is fabricated through bonding of a moulded Polydimethylsiloxane (PDMS) layer to a glass substrate with patterned gold electrodes. The real-time differential measurements let us measure the local drug concentration with accuracies of better than 10pMol/mL. By using the data from all of the array electrodes, the profile of the drug plug as it travels along the microchannel from the injection point to the cell location can be derived with high precision. The multidomain numerical simulations of the microfluidic setup are in line with the measured experimental data. Our technique can be easily integrated into many existing and new designs thus providing a robust approach for label-free measurement of fluid properties in cell viability studies.

Most Lab-on-a-Chip systems require a platform with external supply and control units to be operated. In this manuscript, we report on the development of a modular optoelectronic microfluidic backplane, enabling the flexible interconnection, supply, and control of microfluidic and optofluidic devices. The developed system was fabricated in polymers and consists of backplane modules that may be individually connected with each other. Each module holds one dedicated port on top for a device to be operated. In particular, we introduce an optical backplane module based on a novel optomechanical light switch to guide light to the device of choice within the system. This modular approach allows assembling an arbitrary number of different devices in three dimensions. In conclusion, the backplane provides a configurable platform for multiple optofluidic applications.

A novel hybrid nano/microfabrication technology has been employed to produce unique MEMS and microfluidic components that integrate nanoporous membranes. The components are made by micromachining a self-organized nanostructured ceramic material that is biocompatible and amenable to surface chemistry modification. Microfluidic structures, such as channels and wells, can be made with a precision of <2 microns. Thin-film membranes can be integrated into the bottom of these structures, featuring a wide range of possible thicknesses, from 100 micron to <50 nm. Additionally, these membranes may be non-porous or porous (with controllable pore sizes from 200 nm to <5 nm), for sophisticated size-based separations. With previous and current support from the NIH SBIR program, we have built several unique devices, and demonstrated improved separations, cell culturing, and imaging (optical and electron microscopy) versus standard products. Being ceramic, the material is much more robust to demanding environments (e.g. high and low temperatures and organic solvents), compared to polymer-based devices. Additionally, we have applied multiple surface modification techniques, including atomic layer deposition, to manipulate properties such as electrical conductivity. This microfabrication technology is highly scaleable, and thus can yield low-cost, reliable, disposable microcomponents and devices. Specific applications that can benefit from this technology includes cell culturing and assays, imaging by cryo-electron tomography, environmental sample processing, as well as many others.

We report the demonstration of an optofluidic surface enhanced Raman spectroscopy (SERS) device that leverages nanoporous microfluidics to dramatically increase the SERS performance. A number of optofluidic approaches have been used to improve the detection limit of SERS in microfluidic channels, including active concentration of nanoparticles and/or analyte and passive concentration of nanoparticles. Previous reports have used a single nanofabricated fluidic channel to trap metal nanoparticles and adsorbed analytes. In this work, we utilize a significantly simpler fabrication approach by packing silica beads in a microfluidic channel to create a 3D nanofluidic concentration matrix. The device is fabricated using polydimethylsiloxane (PDMS) on glass using typical soft lithography methods. Due to the larger area of the nanoporous fluidic channel, this approach should be less prone to clogging than single nanofluidic inlets, and the loading time is decreased compared to previous reports. Using this microfluidic device, we achieved a detection limit of 4 femtomoles of Rhodamine 6G in 2 minutes. Compared to an open microfluidic channel, the 3D nanoporous concentration matrix increased the SERS signal by a factor of 250 due to the trapping of silver nanoclusters. Fiber optic cables are integrated into the PDMS to deliver excitation light directly to the detection volume and to collect Raman-scattered photons. As a result, the use of a laser diode and alignment-free integrated fiber optics implies the potential for the device to be used in portable and automated applications, such as the on-site detection of pesticides, water contaminants, and explosives.

Enrichment and separation of cell components of blood is critical to clinical diagnostics and therapeutics. Here we report on spiral inertial microfluidic devices which achieve continuous size-based separation of cell mixtures with high throughput. These devices rely on hydrodynamic forces acting on cells within laminar flow, coupled with Dean instability-induced drag arising from the spiral microchannel geometry, to focus cells in streams near the inner channel wall. The spiral devices were optimized to achieve cell separation in less than 8 cm. These improved devices represent an important development because they are not only small in size (<1 in²), but exhibit high separation efficiency (~90%) and high throughput rates up to 1 million cells per minute. These device concepts offer a path towards possible development of a lab-on-chip for blood analysis and reagent free sample preparation, illustrated by the present results, which successfully demonstrate separation of erythrocytes from leukocytes with whole blood.

We report on the development of a portable fluorescence detection system. By combining a CMOS sensor and crosspolarization scheme, we achieved multiplexed detection with a single white emission LED excitation. We demonstrated fluorescence detection of Fluorescein and Rhodamine B in PDMS channels and achieved 1μM limit of detection (LOD). Microparticles with green and red fluorescence were detected simultaneously without changing the light sources or filters. We were able to clearly resolve microparticles, even if aggregated. The compact microfluorescence approach offers high spatial and spectral resolution, and is suitable for multiplexed detection in point-of-care applications.

In simple microfluidic contraction/expansion geometry, even a dilute polymeric solution is able to exhibit large upstream corner vortices and unstable entry flow patterns at high enough deformation rate (Deborah Number > 200). We have previously demonstrated a similar concept on multiple-stream flow of dissimilar viscoelastic solutions in planar microdevices containing abrupt contraction. Using the same test-vehicle, here we attempt to show that the elasticity ratio between two solutions plays an important role in entire flow kinematics (both upstream and downstream of a contraction) and thus the enhanced mixing of the two solutions. That is the upstream's stretching dynamics induced by the converging flow and the downstream's relaxation events are not exclusively responsible for the multi-stream flow kinematics but the elasticity ratio is also equally important. In this paper, the necessity of elasticity ratio for convective flow instability and the associated enhanced mixing were demonstrated experimentally. Our results show that the magnitude of the viscoelastically induced flow instability can be directly correlated to the energy discontinuity at the stream-stream interfaces at downstream of a contraction. These findings lay the foundation for optimizing the desired mixing quality via viscoelastic flow instability with negligible diffusion and inertial effects. This type of mixing can be achieved over short mixing length at relatively fast flow velocities (~10¹ mm/s) and is postulated to be easily integrated into μTAS platforms due to its simple design.

Usually optofluidic lenses are spherical (ball lenses), plano - concave or plano - convex. Here we present a method to fabricate non - ball small microfluidic lenses in the bulk of a polymer. The cavity of these lenses can be filled with a liquid by means of a syringe. Liquids present different refractive index thus the lens focal distance can be changed at will. An optical characterization study and an application in the measurements of liquids refractive index are shown. Arrays of microfluidic lenses were also fabricated.

This paper describes the simulation and design of a MEMS thermal gyroscope and optimizing the design for increased sensitivity through the use of the Comsol Multiphysics software package. Two different designs are described, and the effects of working fluid properties are explored. A prototype of this device has been fabricated using techniques for rapid prototyping of MEMS transducers.

The performance of interdigitated electrodes for impedance measurements in a microfluidic assay chamber is dependent upon the geometric design of the electrode pattern and can be significantly impacted by variability or defects in manufacturing or materials. For processes which rely on precise electrode performance, it is necessary to minimize variation through robust design and quality control. An interdigitated electrode design was investigated to identify design strategies which maximize electrode sensitivity and minimize performance variability in produced parts, while potentially reducing the complexity of quality testing. Several configurations were developed to address these goals by increasing the sensing region for a specified electrode area and creating designs which can be easily manufactured with low variability. Design modifications included alterations to interdigitated finger orientation, finger geometry, and gap width. Test findings indicate that optimal designs contain narrow gap widths with electrode fingers parallel to the longest dimension of the electrode. These benefits may be further enhanced by replacing straight finger edges with geometrical features, such as scalloped edges. The design changes identified can be used to improve interdigitated electrode performance for an array of applications and to reduce performance variability caused by variation in the manufacturing process.

Due to the ease of fabrication and localized response to stimulus (pH, ionic strength, or heat), many researchers have employed stimuli-responsive hydrogels such as poly(N-isopropylacrylamide) (PNIPAAm) as excellent biocompatible materials for microfluidic actuators. We have previously presented the design and fabrication of a mechanically flexible diaphragm-based actuator by employing a reservoir of thermally responsive hydrogel PNIPAAm and a conductive nanocomposite polymer (C-NCP) heater element. We now present the construction, characterization, and simulation of a hydrogel-based microvalve and its application for flow control with a new inexpensive and efficient flexible heater. In this work, we have fabricated the microvalve using traditional microfabrication and soft lithography processes. We accurately pattern and insert the hydrogel plug structure as a fluidic control component within a microfluidic channel. We demonstrate that swelling and shrinking of the hydrogel plug in the microchannel results in closing and opening of the valve. New simulations of the hydrogel plug design were employed using COMSOL® Multiphysics to show the pressure distribution and hydrogel plug movement as well as fluidic velocity in the simulated channel. We then compare the theoretical computed value with the prediction of the COMSOL simulation result which verifies the functionality of our hydrogel plug microvalve design.

Interdigitated electrodes are used as sensing components in microfluidic lab-on-a-chip devices. The Daktari Diagnostics system uses electrodes to measure the change in impedance of a fluid in an assay chamber. A new testing method was developed and validated to characterize the sources of defects in electrodes and used to validate a new manufacturing process. The impedance of an electrode-in-solution system for solutions of different known conductivities was measured. The characteristic linear relationship (slope) between the inverse of the impedance to the solution conductivities was estimated. Repeatability tests found an average slope of 1.438x10-5 (1/Ω)/(μS/cm) - or cm/characteristic length - with a standard deviation of 8.52x10-8 cm/characteristic length. The impact of defective electrode fingers and mechanical bending on electrode performance was characterized.