This PDF file contains the front matter associated with SPIE Proceedings Volume 7929, including the Title Page, Copyright information, Table of Contents, and Conference Committee listing.

Yogi Berra once noted that "You can observe a lot just by watching." A similar remark can be made about toys: you can learn a lot of physics by playing with certain children's toys, and given that physics also applies to life, you could hope that it would also be possible to learn about the physics of living cells by close observation of toys, loosely defined. I'll start out with a couple of toys, rubber duckies and something called a soliton machine and discuss insights (or failures) in how "energy" moves in biological molecules. I'll bring back the rubber duckies and a toy suggested by one of the eccentrics known to roam the halls of academia to discuss how this lead to studies how cells move and collective aspects of cell movement. Then I'll talk about mazes and how they lead to experiments on evolution and cancer. Hopefully this broad range of toys will show how indeed "You can observe a lot just by watching" about some of the fundamental physics of living cells.

Lab-on-a-chip systems are seen as a very promising approach for a decentralized continuous pathogen monitoring technology. In this paper, we present the development of a fully integrated device for the multiplexed nucleic-acid based identification of pathogens. Due to the complexity of such a fully integrated device, in a first development step, functional modules for the various process steps like lysis, DNA extraction and purification, continuous-flow PCR and detection have been developed and evaluated, allowing a functional verification prior to integration. All the modules as well as the final integrated device have been manufactured using scaleable industrial manufacturing methods, namely injection molding in order to facilitate commercialization.

Metastatic cancer cells respond to chemical and mechanical stimuli in their microenvironment that guide invasion into the surrounding tissue and eventually the circulatory/lymph systems. The NANIVID is designed to be an in vivo device used to collect metastatic cancer cells by providing a gradient of epidermal growth factor through the controlled release from a customized hydrogel. The model cells, MTLn3 and Mena^Inv, both derived from a rat mammary adenocarcinoma, will migrate toward the device and be collected in the chamber. A set of electrodes inside the chamber will provide real-time data on the density of cells collected in the device. The characterization and optimization of the electrodes in vitro will be reported, as will the development of an equivalent circuit model used to describe electrode behavior. The ultimate goal of this work is for the NANIVID to be used for in vivo investigations of a rat model of mammary cancer. Furthermore, since the morphology, mechanical properties, and movement of cells are influenced by the microenvironment, a combined scanning confocal laser microscope and atomic force microscope will be used to study these relationships. This work will further the understanding of the dynamics and mechanics of metastatic cancer cells as they leave the primary tumor and metastasize.

This research involves a new approach for the study of the mechanical properties of single living cells. The main idea is to use micro electro mechanical systems (MEMS) to investigate the Young modulus and the morphological modification of cells from the engineering point of view. Many different techniques already exist for a local cell analysis but our goal is to be able to test the properties of a single adherent cell in his complexity. We realized a completely transparent device which is versatile and can be coupled with other analysis tools such as atomic force microscopy (AFM) and patch clamp. Starting from a transparent wafer we developed a system to obtain high transparency suspended structures. All structures are made by using micro fabrication techniques. Our MEMS is composed by 3 main parts: (i) testing, (ii) measurement and (iii) actuation area.

In this work we describe the use of inertial microfluidics for continuous multi-particle separation in a simple spiral microchannel. The inertial forces coupled with the rotational Dean drag force in the spiral microchannel geometry cause neutrally-buoyant particles and cells to occupy a single equilibrium position near the inner microchannel wall. This position is strongly dependent on the particle/cell diameter. Based on this concept, a 5-loop Archimedean spiral microchannel chip was used to demonstrate for the first time focusing and separation of four particles simultaneously. The polystyrene particles (7.32 μm, 10 μm, 15 μm, 20 μm in diameter) were selected for this work since they are compatible to the size of blood cells. The device exhibited an average 87% separation efficiency, which is comparable to that of other microfluidic separation systems. The simple planar structure and high sample throughput offered by this passive microfluidic approach makes it attractive for lab-on-a-chip integration in hematology applications.

The development of a polydimethylsiloxane (PDMS) microfluidic microbeads trapping device is reported in this paper. Besides fluid channels, the proposed device includes a pneumatic control chamber and a beads-trapping chamber with a filter array structure. The pneumatic flow control chamber and the beads-trapping chamber are vertically stacked and separated by a thin membrane. By adjusting the pressure in the pneumatic control chamber, the membrane can either be pushed against the filter array to set the device in "trapping mode" or be released to set the device in "releasing mode". In this paper, a computational fluid dynamics simulation was conducted to optimize the geometry design of the filter array structure; the device fabrication was also carried out. The prototype device was tested and the preliminary experimental results showed that it can be used as a beads-trapping unit for various biochemistry and analytical chemistry applications, especially for flow injection analysis systems.

The optical propulsion of mammalian eukaryotic cells along the surface of an integrated channel waveguide is demonstrated. 10μm diameter polymethylmethacrylate (PMMA) spherical particles and similarly sized mammalian eukaryotic cells in aqueous medium are deposited in a reservoir over a caesium ion-exchanged channel waveguide. Light from a fibre laser at 1064nm was coupled into the waveguide, causing the polymer particles or cells to be propelled along the waveguide at a velocity which is dependent upon the laser power. A theoretical model was used to predict the propulsion velocity as a function of the refractive index of the particle. The experimental results obtained for the PMMA particles and the mammalian cells show that for input powers greater than 50mW the propulsion velocity is approximately that obtained by the theoretical model. For input powers of less than ~50mW neither particles nor cells were propelled; this is considered to be a result of surface forces (which are not considered in the theoretical model). The results are discussed in light of the potential application of optical channel waveguides for bioanalytical applications, namely in the identification and sorting of mammalian cells from mixed populations without the need for fluorescence or antibody labels.

Cancer cells create a unique microenvironment in vivo which enables migration to distant organs. To better understand the tumor microenvironment, special tools and devices are required to monitor the interactions between different cell types and the effects of particular chemical gradients. This study presents the design and optimization of a new, versatile chemotaxis device called the NANIVID (NANo IntraVital Device). The device is fabricated using BioMEMS techniques and consists of etched and bonded Pyrex substrates, a soluble factor reservoir, fluorescent tracking beads and a microelectrode array for cell quantification. The reservoir contains a customized hydrogel blend loaded with EGF which diffuses out of the hydrogel to create a chemotactic gradient. This reservoir sustains a steady release of growth factor into the surrounding environment for many hours and establishes a concentration gradient that attracts specific cells to the device. In addition to a cell collection tool, the NANIVID can be modified to act as a delivery vehicle for the local generation of alternate soluble factor gradients to initiate controlled changes to the microenvironment such as hypoxia, ECM stiffness and etc. The focus of this study is to design and optimize the new device for wide ranging studies of breast cancer cell dynamics in vitro and ultimately, implantation for in vivo work.

Due to a number of recent technological advances, a hand-held flow cytometer can be achieved by use of semiconductor illuminators, optical sensors (all battery powered) and sensitive cell markers such as immuno-quantum dot (Qdot) labels. The specific application described is of a handheld blood analyzer that can quickly process a drop of whole, unfractionated human peripheral blood by real-time, on-chip magnetic separation of white blood cells (WBCs) and red blood cells (RBCs) and further fluorescence analysis of Qdot labeled WBC subsets. Various microfluidic patterns were fabricated in PDMS and used to characterize flow of single cells and magnetic deflection of magnetically labeled cells. An LED excitation, avalanche photodiode detection system (SensL Technologies, Ltd., Cork, Ireland) was used for immuno-Qdot detection of WBC subsets. A static optical setup was used to determine the sensitivity of the detection system. In this work we demonstrate: valve-less, on-chip magnetic sorting of immunomagnetically labeled white blood cells, bright Qdot labeling of lymphocytes, and counting of labeled white blood cells. Comparisons of these results with conventional flow cytometric analyses are reported. Sample preparation efficiency was determined by labeling of isolated white blood cells. Appropriate flow rates were determined for optical detection and confirmed with flowing particles. Several enabling technologies required for a truly portable, battery powered, hand-held flow cytometer for use in future point-of-care diagnostic devices have been demonstrated. The combining of these technologies into an integrated handheld instrument is in progress and results on whole blood cell analysis are to be reported in another paper.

In this paper we demonstrate the development of an integrated lab-on-a-chip system for the point-of-care diagnostics of Coeliac disease. A two-step approach is used, using two different microfluidic chips with identical footprint and functional landscape, one for the analysis of the genetic predisposition using human leukocyte antigen typing, the second for a serology assay. Emphasis has been put on using a seamless technology path from prototyping to final device manufacture in order to allow an upscaling of production volumes without a chance in production technology. Therefore, injection molding has been extensively used, however using standard formats allowing the use of family tools in order to reduce the cost of manufacturing.

Taking advantage of microfluidics technology, a Lab-on-Chip system was developed offering the possibility of performing HLA (Human Leukocyte Antigen) typing to test genetic predisposition to coeliac disease and measure the level of immunodeficiency at the point-of-care. These analysis procedures are implemented on two different microfluidic cartridges, both having identical interfacial connections to the identical automated instrument. In order to assess the concentration of the targeted analytes in human blood, finger prick samples are processed to either extract genomic DNA carrying the coeliac disease gene or blood plasma containing the disease specific antibodies. We present here the different microfluidic modules integrated in a common platform, capable of automated sample preparation and analyte detection. In summary, this new microfluidic approach will dramatically reduce the costs of materials (polymer for the disposable chips and minute amount of bio-reagents) and minimize the time for analysis down to less than 20 minutes. In comparison to the state of the art detection of coeliac disease this work represents a tremendous improvement for the patient's quality of live and will significantly reduce the cost burden on the health care system.

Microscale liquid handling based on electrowetting has been previously demonstrated by several groups. Such liquid manipulation however is limited to control of individual droplets, aptly termed digital microfluidics. The inability to form continuous channels thus prevents conventional microfluidic sample manipulation and analysis approaches, such as electroosmosis and electrophoresis. In this paper, we discuss our recent progress on the development of electrowettingbased virtual channels. These channels can be created and reconfigured on-demand and preserve their shape without external stimulus. We also discuss recent progress towards demonstrating electroosmotic flows in such microchannels for fluid transport. This would permit a variety of basic functionalities in this new platform including sample transport and mixing between various functional areas of the chip.

We present the design, fabrication and characterization of a mechanically flexible diaphragm-based microvalve actuator employing a reservoir of the thermally responsive hydrogel PNIPAAm and a conductive nanocomposite polymer (C-NCP) heater element. The microvalve actuator can be fabricated employing traditional soft lithography processes for fabrication of all components, including the tungsten-based C-NCP heater element, the hydrogel reservoir, and the deflecting polymer membrane. Shrinking of the hydrogel under the application of heat supplied by the flexible heater, or the removal of this thermal energy by turning off the heater, forces the diaphragm to move. The silicone diaphragm actuator is compatible with a normally-closed polymer microvalve design where-by the fluidic channel can be opened and closed via the hydrogel diaphragm actuator, in which the hydrogel is normally swollen and heating opens the valve via membrane deflection. Our prototype hydrogel actuator diaphragms are between 100-200 micrometers in diameter, and experimentally deflect approximately 100 micrometers under heating to 32 degrees ºC or above, which is sufficient to theoretically open a microvalve to allow flow to pass through a 100 micrometer deep channel. We characterize the flexible tungsten C-NCP heaters for voltage versus temperature and show that the flexible heaters can reach the hydrogel transition temperature of 32 degrees °C at approximately 13-15 V. We further characterize the hydrogel response to heat, and diaphragm deflection using both hot plate and flexible C-NCP heater elements. While our results show diaphragm deflection adequate for microvalves at a reasonable voltage, the speed of deflection is currently very slow and would result in slow microvalve response speed (30 seconds to open the valve, and 120 seconds to reclose it).

We present the design, fabrication and characterization of a novel bidirectional magnetic microactuator. The actuator has a planar structure and is easily fabricated using processes based on laser micromachining and soft lithography, allowing it to be readily integrated into microfluidic, microelectromechanical systems (MEMS) and lab-on-a-chip (LOC) designs. The new microactuator is a thin magnetic membrane with a central magnet feature. The membrane and magnet are both composed of a magnetic nanocomposite polymer (M-NCP) material that is fabricated by embedding magnetic powder in a polydimethysiloxane (PDMS) polymer matrix. The magnetic powder (MQP-12-5) has the chemical composition of (Nd0.7Ce0.3)10.5Fe83.9B5.6, and contains grains that are 5-6 microns in size. The powder is uniformly dispersed at a weight percentage of 75 wt-% in the PDMS matrix, and micropatterned using soft lithography micromolding to realize magnetic microstructures, which sit on a thinner magnetic PDMS membrane of the same material. The molds are fabricated by laser-etching into Poly (methyl methacrylate) (PMMA) using a Universal Laser System's VersaLASER© laser ablation system. The PDMS-based M-NCP is then poured and spun over the mold patterns, producing a thin polymer membrane to which the polymer micromagnets are attached, forming a one-piece actuator. The M-NCP is initially un-magnetized, but is then magnetized by placing it in a 2.5T magnetic field to produce permanent bidirectional magnetization that is polarized in the specified direction. To characterize the bidirectional actuators, a uniform magnetic field is established via a Helmholtz coil pair, and is characterized by applying varying currents. The magnetic field (and thus the actuator deflection) is controlled by regulating the current in the Helmholtz pair. Using this apparatus, deflection versus field characteristics are obtained, with maximum deflections varying as a function of actuator dimensions and the applied magnetic field. Permanent rare earth magnets are used to produce supplemental fields for higher magnetic fields and higher deflections. Deflections of 100 micrometers and more are observed for 3 to 8 mm square membranes with central magnetic features ranging from 0.8 to 3.6 mm squares, in magnetic fields ranging from 52 to 6.2 mT. In addition, smaller membranes (1 mm and 2 mm with 0.4 mm and 0.6 mm central magnets, respectively) also deflect 20 and 50 microns, respectively, under 72 mT fields.

Silicon-On-Insulator (SOI) photonic microring resonators have shown promising potential for real time detection of biomolecules because of the sensitivity towards surface binding events. Previous work shows the use of single ring resonators for sensing applications. Each ring requires an input and output coupler and can be addressed only one at a time. We propose a novel use of cascaded ring resonators (width w = 200 nm and bending Radius R = 30 μm) together with a PDMS microfluidic network fabricated by soft lithography to expose each ring individually with different solutions. The SOI substrate with the planar waveguides and the PDMS with the microchannels are reversibly bonded to each other. The use of cascaded ring resonators offers the possibility to measure transmission spectra of multiple rings in different channels simultaneously. We measured Q-factors of >30'000 in air and >10'000 when exposed to water. Using a water/glycerin solution with known refractive indices we determine the sensitivity to be ~40 nm/RIU.

A computational study of peristaltic micropumps is presented. The peristaltic micropump considered in this study consists of two to five chambers in series which rectify the flow by means of both peristaltic movement of actuators and diffuser/nozzle elements. We consider a closed loop configuration in order to reduce the error introduced by presence of inlet/outlet boundary conditions. The characteristics of these pumps such as maximum volume flux and pressure drop were investigated. In addition, the viability of such pumps to work with cells was examined by calculating the maximum shear stress and strain rate.

A computational analysis of a microchannel reacting flow that includes diffusion and heat transfer processes to determine design rules for sensor placement is described. The objective is to optimize the positioning of nanohole array sensors which measure concentration and temperature and to analyze the characteristics of the local quantities sensed by nanohole arrays. Because the position and minimum spacing of the sensors are limited by material and fabrication constraints, the computational analysis is used to verify the effectiveness and limitations of this approach. Thermal boundary analysis is performed to analyze the relation between the sensed layer (micro-sensing region) over the nanohole array sensors and the boundary layer development. The relationship between the sensor position and the nodes of the numerical solution that limit this design process are discussed.

Microfluidic systems have faced challenges in handling real samples and the chip interconnection to other instruments. Here we present a simple interface, where surface acoustic waves (SAWs) from a piezoelectric device are coupled into a disposable acoustically responsive microfluidic chip. By manipulating droplets, SAW technologies have already shown their potential in microfluidics, but it has been limited by the need to rely upon mixed signal generation at multiple interdigitated electrode transducers (IDTs) and the problematic resulting reflections, to allow complex fluid operations. Here, a silicon chip was patterned with phononic structures, engineering the acoustic field by using a full band-gap. It was simply coupled to a piezoelectric LiNbO3 wafer, propagating the SAW, via a thin film of water. Contrary to the use of unstructured superstrates, phononic metamaterials allowed precise spatial control of the acoustic energy and hence its interaction with the liquids placed on the surface of the chip, as demonstrated by simulations. We further show that the acoustic frequency influences the interaction between the SAW and the phononic lattice, providing a route to programme complex fluidic manipulation onto the disposable chip. The centrifugation of cells from a blood sample is presented as a more practical demonstration of the potential of phononic crystals to realize diagnostic systems.

A design incorporating surface plasmon resonance (SPR) biosensing and surface acoustic wave (SAW) active microfluidic mixing, integrated on a single LiNbO₃ piezoelectric substrate, is presented. Validation experiments show that SAW-mixing (microstreaming) results in accelerated binding kinetics (time-to-saturation) for a standard assay with appropriate SAW excitation parameters. Since both SPR sensors and SAW transducers can be fabricated simultaneously using low-cost microfabrication methods, the proposed design should contribute to improved lab-on-chip devices for detecting and identifying biomolecules of interest with greater accuracy and speed across multiple applications.

In this work we present the first approach towards low-cost free-flow electrophoresis (FFE) devices utilizing injection molding as a microfabrication process which has the potential to manufacture FFE chips at a cost which make their use commercially viable. This is achieved by realizing a new straightforward micro free-flow electrophoresis (μFFE) design ensuring both, bubble free electrophoretic separation and effective electrical connection by implementing miniaturized partitioning bars. This creates a defined open gap of 20 μm in height and 500 μm in width between separation zone and electrode channels. The thermoplastic μFFE chips are ready to use, there is no need for a subsequent labor-intensive implementation of membranes or salt bridges to separate the electrode channels from the separation zone.

A continuous flow microfluidic cell separation platform has been designed and fabricated using femtosecond laser inscription. The device is a scalable and non-invasive cell separation mechanism aimed at separating human embryonic stem cells from differentiated cells based on the dissimilarities in their cytoskeletal elasticity. Successful demonstration of the device has been achieved using human leukemia cells the elasticity of which is similar to that of human embryonic stem cells.

Metallic nanohole arrays support surface electromagnetic waves that enable enhanced optical transmission and may be exploited for sensing. Our group has been active in the application of enhanced optical transmission to chemical and biological sensing, and in the optofluidic integration nanohole arrays. Our recent work in this area is described here. Our research on the combined photonic and fluidic characteristics of flow-through nanohole arrays and their application to sensing is presented. Flow-through nanohole arrays provide a biomarker sieving capacity that is unique among plasmonic sensors as well as rapid transport of reactants to the sensing surface. Our experiments indicate a order of magnitude improvement in sensor response time for flow-through operation as compared to current flow-over sensing methods. Transport analysis results indicate that more than a 20-fold improvement may be expected for small biomolecules with rapid reaction kinetics.

The aim of this paper is to demonstrate the feasibility of an implantable, low voltage driven microfluidic pump to deliver drugs. The micro pump has a high degree of biocompatibility and mechanical deformation capability, thanks to the use of elastic silicone elastomers (PDMS) for integration and embedding of the pump. We are using the new method of transverse DC electro-osmosis, which is demonstrated already in the literature. The method uses the fabrication of periodic grooves on top of the micro channel and the application of a DC voltage across the channel. In this contribution, for the first time the production and operation of soft elastic versions of such a pump, compatible with body tissue, is demonstrated. For the interconnects, gold is selectively electro-deposited on Cu-foil and is transferred to PDMS layer. Having only gold as the interconnect ascertains the high degree of bio-compatibility of the device. This pump works with voltages about 10V and produces mean flow speeds of about 60μm/s. The flow has also a helical profile which is a very good advantage to use this pump as a mixer for micro fluidic applications. Flow rate is measured by introducing dyed micro particles along with the liquid inside the channel.

We have developed a fully automated platform for multiparameter characterization of physiological response of individual and small numbers of interacting cells. The platform allows for minimally invasive monitoring of cell phenotypes while administering a variety of physiological insults and stimuli by means of precisely controlled microfluidic subsystems. It features the capability to integrate a variety of sensitive intra- and extra-cellular fluorescent probes for monitoring minute intra- and extra-cellular physiological changes. The platform allows for performance of other, post- measurement analyses of individual cells such as transcriptomics. Our method is based on the measurement of extracellular metabolite concentrations in hermetically sealed ~200-pL microchambers, each containing a single cell or a small number of cells. The major components of the system are a) a confocal laser scan head to excite and detect with single photon sensitivity the emitted photons from sensors; b) a microfluidic cassette to confine and incubate individual cells, providing for dynamic application of external stimuli, and c) an integration module consisting of software and hardware for automated cassette manipulation, environmental control and data collection. The custom-built confocal scan head allows for fluorescence intensity detection with high sensitivity and spatial confinement of the excitation light to individual pixels of the sensor area, thus minimizing any phototoxic effects. The platform is designed to permit incorporation of multiple optical sensors for simultaneous detection of various metabolites of interest. The modular detector structure allows for several imaging modalities, including high resolution intracellular probe imaging and extracellular sensor readout. The integrated system allows for simulation of physiologically relevant microenvironmental stimuli and simultaneous measurement of the elicited phenotypes. We present details of system design, system characterization and metabolic response analysis of individual eukaryotic cells.

We designed, built, tested, space-qualified, launched, and collected telemetered data from low Earth orbit from Pharma- Sat, a 5.1-kg free flying "nanosatellite" that supported microbial growth in 48 microfluidic wells, dosed microbes with multiple concentrations of a pharmaceutical agent, and monitored microbial growth and metabolic activity using a dedicated 3-color optical absorbance system at each microwell. The PharmaSat nanosatellite comprised a structure approximately 10 x 10 x 35 cm, including triple-junction solar cells, bidirectional communications, power-generation and energy- storage system, and a sealed payload 1.2-L containment vessel that housed the biological organisms along with the fluidic, optical, thermal, sensor, and electronic subsystems. Growth curves for S. cerevisiae (Brewer's yeast) were obtained for multiple concentrations of the antifungal drug voriconazole in the microgravity conditions of low Earth orbit. Corresponding terrestrial control experiments were conducted for comparison.

With the increasing interest in the exploitation of micro-reactors, there is a growing demand for process monitoring and control methods suitable for application in this environment. At present off-line analysis methods such as chromatography and mass spectrometry are the dominant tools in the field. Although these methods provide exceptionally rich chemical information they require removal of samples from the system and the analysis is not instantaneous. In many microfluidic applications these limitations outweigh their benefits due to the importance of real-time detection and the desired ability to analyze the fluid in different locations in the micro-reactor non-invasively. Therefore optical detection methods such as fluorescence and Raman spectroscopy are becoming increasingly popular in this field, with most attention being drawn to miniature integrated optical sensors. However, integration of sensors into a micro-reactor can change the flow conditions and make the system difficult to scale out. It is also impossible to move the integrated sensor along the flow path. These issues make on-chip process analysis a challenging subject that is still at the early stages of development. This paper discusses opportunities for non-invasive process analysis in micro-reactors focusing the main attention on Raman spectrometry as a powerful technique, whose potential in this field has not been widely recognized yet. With a specially developed probe we demonstrate ability to monitor fluid delivery stability and perform fast real-time analysis of a model esterification reaction. The discussed approach brings unique benefits to kinetics studies, efficient process optimization and process control.

Interactions of NEMS with fluids are of interest both in determining the NEMS performance outside of vacuum, and in elucidation of fluid dynamics at these small scales. We present a comprehensive study of nanomechanical damping in three gases (He, N₂, CO₂), and liquid CO₂. Resonant dynamics in multiple devices of varying size and frequency (10-400 MHz) is measured over 10 decades of pressure (1 mPa-20 MPa). We find a fluid relaxation time model to be valid throughout, but not beyond, the non-Newtonian regime (up to several atmospheres), and classical vibrating spheres model to be valid in the viscous limit.

In this study, we investigate a simple, disposable, low-cost, ultrasensitive, and fully-integrated biosensor chip for early ovarian cancer detection. The proposed sensor quantifies urinary anti-apoptotic protein Bcl-2 level that is elevated at various stages of ovarian cancer. Our approach utilizes MEMS ultrasonic transducers that have been demonstrated to be advantageous when compared to piezoelectric transducers. Piezoelectric transducers are expensive, bioincompatible (contain lead), and cannot be integrated in a fully-packaged chip. More importantly, these transducers lack the sensitivity required for early ovarian cancer detection, expensive, not biocompatible (contains Lead) and cannot be integrated for a fully-packaged chip. Our experimentally verified simulations indicate 0.15 pg/ml mass sensitivity with our sensor.

Effective host-local system architecture for PCR chips is presented. The functions required for the control of the chips and their partitioning into the host and the local system are qualitatively analyzed. The results indicated that, most functions can be resided in the host to deliver the benefits on the development period, the system cost, and the maintenance. The control system was implemented with PC as the host and the local system was connected by USB interface, obtaining the superior development and the GUI design environment. A PCB-based PCR chip example was constructed and tested to verify the proposed system.

We present initial results on the fabrication and testing of micropatternable conductive nanocomposite polymer (C-NCP) electrodes for tissue impedance measurements. We present these proof-of-concept results as a first step toward the realization of our goal: an improved Electrical Impedance Scanning (EIS) system, whereby tissue can be scanned for cancerous tissue and other anomalies using large arrays of highly flexible microfabricated electrodes. Previous limitations of existing EIS system are addressed by applying polymer based microelectromechanical system (MEMS) technology. In particular, we attempt to minimize mechanical skin contact issues through the use of highly compliant elastomeric polymers, and increase the spatial resolution of measurements through the development of microelectrodes that can be micropatterned into large, highly dense arrays. We accomplish these improvements through the development of C-NCP electrodes that employ silver nanoparticle fillers in an elastomer polymer base that can be easily patterned using conventional soft lithography techniques. These new electrodes are tested on conventional tissue phantoms that mimic the electrical characteristics of human tissue. We characterize the conductivity of the electrodes (average resistivity of 7x10^-5 ohm-m +/- 14.3% at 60 wt-% of silver nanoparticles), and further employ the electrodes for impedance characterization via Cole-Cole plots to show that measurements employing C-NCP electrodes are comparable to those obtained with normal macroscopic metal electrodes. We also demonstrate anomaly detection using our highly flexible Ag/AgCl C-NCP electrodes on a tissue phantom.

Template matching method is presented to identify the peaks from the scanned signals of lateral flow immunoassay strips. The template is composed of two pulses separated by the distance of the control and the target ligand line in the assay, and is convolved with the scanned signal to deliver the maximum at the center of the two peaks. The peak regions were identified with the predefined distances from the center. Glycosylated haemoglobin immunoassay strips and fluorescent strip readers from Boditechmed Inc. were tested to estimate the lot and reader variations of the concentration measurands. The results showed the robustness of the propose method.