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In this work we present the results obtained on the simulation and nanofabrication of photonic crystals based on silicon nanopillars. The simulations show the formation of photonic band gaps within 1.31 and 1.89μm, with a gap-to-midgap ratio approaching 40%. The introduction of waveguides and cavities prove the adaptability of these structures to tune the wavelengths allowed to be transmitted through the system within the photonic band gaps. On the other hand, thanks to the use of advanced nanofabrication techniques, the modelled structures have been successfully fabricated.

A graphical user interface (GUI) with Tkinter was created in Python to facilitate data analysis for electrochemical techniques in cyclic voltammetry and electrochemical impedance. The GUI lets the user select a technique, measurement(s), and eventually customize the plots.

Lateral flow assays (LFAs) are low-cost testing tools widely used for home, point-of-care, or laboratory medical diagnostics. These tests typically use colorimetry to report the presence and the concentration of a certain physical/ biological quantity, showing the result as a color marker. This work presents a computer vision algorithm for the digitalization of LFA readouts, enabling precise and reliable results at low-cost. The algorithm receives as input an image of a sample, identifies the color marker, and computes its average color intensity. In contrast to existing algorithms, the proposed one can detect color markers that are not characterized by a predetermined precise shape, size, and position, since the topology is identified and analyzed by the algorithm itself. The evaluation of the proposed algorithm on a set of LFA strips shows correct functionality and execution time of less than a second.

Next‐generation genome sequencing machines and Point‐of‐Care (PoC) in vitro diagnostics devices are precursors of an emerging class of Cyber‐Physical Systems (CPS), one that harnesses biomolecular‐scale mechanisms to enable novel "wet‐technology" applications in medicine, biotechnology, and environmental science. Although many such applications exist, testifying the importance of innovative life‐sciences instrumentation, recent events have highlighted the difficulties that designing organizations face in their attempt to guarantee safety, reliability, and performance of this special class of CPS. New regulations and increasing competition pressure innovators to rethink their design and engineering practices, and to better address the above challenges. The pace of innovation will be determined by how organizations manage to ensure the satisfaction of aforementioned constraints while also streamlining product development, maintaining high cost‐efficiency and shortening time‐to‐market. Model‐Based Systems Engineering provides a valuable framework for addressing these challenges. In this paper, we demonstrate that existing and readily available model‐based development frameworks can be adopted early in the life‐sciences instrumentation design process. Such frameworks are specifically helpful in describing and characterizing CPS including elements of a biological nature both at the architectural and performance level. We present the SysML model of a smartphone‐based PoC diagnostics system designed for detecting a particular molecular marker. By modeling components and behaviors spanning across the biological, physical‐nonbiological, and computational domains, we were able to characterize the important systemic relations involved in the specification of our system's Limit of Detection. Our results illustrate the suitability of such an approach and call for further work toward formalisms enabling the formal verification of systems including biomolecular components.

As a result of biological sciences becoming more quantitative together with the growing economical and societal challenges of improving our health care system, we have witnessed an increasing interest in developing new technologies for the biomedical field. Cyber-medical systems are the fusion of computational and medical technologies aimed to support health management for diagnosis, monitoring, and prevention of diseases. With the advent of miniaturized biochemical laboratories, the classical bench-sized lab robots have transformed into chip-sized complex biochemical laboratories. This development has allowed integration of classical computation with biochemical processes to a degree where computations are moving small amounts of liquids. In this chapter, we survey state-of-the-art microfluidic technologies and argue that even though their applications are still limited to simple passive and fixed structures, they hold the promises of solving many challenging and complex problems related to healthcare. We argue that liquid handling technologies have the potential to scale, but this will require utilization of active components and the ability to abstract their basic operations to a level similar to that of classical computation, i.e., we need to build the equivalent of a general purpose processor—a lab-on-chip (or a biochip) which can be programmed and re-programmed.

Bentazone is one of the most problematic pesticides polluting groundwater resources. It is on the list of pesticides that are mandatory to analyze at water work controls. The current pesticide measuring approach includes manual water sampling and time-consuming chromatographical quantification of the bentazone content at centralized laboratories. Here, we report the use of an electrochemical approach for analytical determination of bentazone that takes 10 s. The electrochemical electrodes were manually screen printed, resulting in the low-cost fabrication of the sensors. The current response was linearly proportional to the bentazone concentration with a R2 ~ 0.999. We demonstrated a sensitivity of 0.0987 μA/μM and a limit of detection of 0.034 μM, which is below the U.S. Health Advisory level. Furthermore, the sensors have proved to be reusable and stable with a drop of only 2% after 15 times reuse. The sensors have been applied to successfully quantify bentazone spiked in real groundwater and lake water. The sensing method presented here is a step towards on-site application of electrochemical detection of pesticides in water sources. Keywords: Bentazone, Sensor, Groundwater, Electrochemistry, Pesticide, Contamination

Miniaturizing the traditional wet lab processes and realizing the full potential of lab-on-a-chip technology (LOC) has been a great challenges for scientists and engineers in the quest of providing health care where such does not exists, or to increase lab efficiency and lower the operational cost. A range of practical LOC fabrication technologies has already been demonstrated, and as a result, the research of real life applications has been steadily increasing. However, due to the variety of used technologies and LOC form factors, it often requires a modification or even a complete redesign of the available instrumentation systems. Standardization and flexible instrumentation has seen limited development in the LOC field even though developing on all application levels has been proven as an effective way to stimulate a growth in a research field. To address this, we present a modular digital microfluidics (DMF) instrumentation platform and a concept of integrated chip-instrument co-design that has the potential to solve a wide range of LOC instrumentation challenges.

This work describes an improvement in the layout of coplanar electrodes for electrical impedance spectroscopy. We have developed, fabricated, and tested an improved electrode layout, which improves the sensitivity of an impedance flow cytometry chip. The improved chip was experimentally tested and compared to a chip with a conventional electrode layout. The improved chip was able to discriminate 0.5 mu m beads from 1 mu m as opposed to the conventional chip. Furthermore, finite element modeling was used to simulate the improvements in electrical field density and uniformity between the electrodes of the new electrode layout. Good agreement was observed between the model and the obtained experimental results.

Although silicon nanowire biological field-effect transistors (SiNW-bioFETs) have steadily demonstrated their ability to detect biological markers at ultra-low concentration, they have not yet translated into routine diagnostics applications. One of the challenges inherent to the technology is that it requires an instrumentation capable of recovering ultra-low signal variations from sensors usually designed and operated in a highly resistive configuration. Often overlooked, the SiNW-bioFET/instrument interactions are yet critical factors in determining overall system biodetection performances. Here, we carry out, for the first time, the system-level sensitivity analysis of a generic SiNW-bioFET model coupled to a custom-design instrument based on the lock-in amplifier. By investigating a large parametric space spanning over both sensor and instrumentation specifications, we demonstrate that system-wide investigations can be instrumental in identifying the design trade-offs that will ensure the lowest limits of detection. The generic character of our analytical model allows us to elaborate on the most general SiNW-bioFET/instrument interactions and their overall implications on detection performances. Our model can be adapted to better match specific sensor or instrument designs to either ensure that ultra-high sensitivity SiNW-bioFETs are coupled with an appropriately sensitive and noise-rejecting instrumentation, or to best tailor SiNW-bioFET design to the specifications of an existing instrument.

The association of smart mobile devices and lab-on-chip technologies offers unprecedented opportunities for the emergence of direct-to-consumer in vitro medical diagnostics applications. Despite their clear transformative potential, obstacles remain to the large-scale disruption and long-lasting success of these systems in the consumer market. For instance, the increasing level of complexity of instrumented lab-on-chip devices, coupled to the sporadic nature of point-of-care testing, threatens the viability of a business model mainly relying on disposable/consumable lab-on-chips. We argued recently that system evolvability, defined as the design characteristic that facilitates more manageable transitions between system generations via the modification of an inherited design, can help remedy these limitations. In this paper, we discuss how platform-based design can constitute a formal entry point to the design and implementation of evolvable smart device/lab-on-chip systems. We present both a hardware/software design framework and the implementation details of a platform prototype enabling at this stage the interfacing of several lab-on-chip variants relying on current- or impedance-based biosensors. Our findings suggest that several change-enabling mechanisms implemented in the higher abstraction software layers of the system can promote evolvability, together with the design of change-absorbing hardware/software interfaces. Our platform architecture is based on a mobile software application programming interface coupled to a modular hardware accessory. It allows the specification of lab-on-chip operation and post-analytic functions at the mobile software layer. We demonstrate its potential by operating a simple lab-on-chip to carry out the detection of dopamine using various electroanalytical methods.

Scalability is a design principle often valued for the engineering of complex systems. Scalability is the ability of a system to change the current value of one of its specification parameters. Although targeted frameworks are available for the evaluation of scalability for specific digital systems, methodologies enabling scalability analysis of multidomain, complex systems, are still missing. In acknowledgment of the importance for complex systems to present the ability to change or evolve, we present in this work a systemlevel model-based methodology allowing the multidisciplinary parametric evaluation of scalability. Our approach can be used to determine how a set of limited changes to targeted system modules could affect design specifications of interest. It can also help predict and trace system bottlenecks over several product generations, offering system designers the chance to to better plan re-engineering efforts for scaling a system specification efficaciously. We demonstrate the value of our methodology by investigating a smartphone-based biosensing instrumentation platform. Specifically, we carry out scalability analysis for the system’s bandwidth specification: the maximum analog voltage waveform excitation frequency the system could output while allowing continuous acquisition and wireless streaming of bioimpedance measurements. We rely on several SysML modelling tools, including dependency matrices, as well as a fault-detection Simulink Stateflow executable model to conclude on how the successive re-engineering of 5 independent system modules, from the replacement of a wireless Bluetooth interface, to the revision of the ADC sample-and-hold operation could help increase system bandwidth.

Lab-on-Chip technologies offer great opportunities for the democratization of in-vitro medical diagnostics to the consumer-market. Despite the limitations set by the strict instrumentation and control requirements of certain families of these devices, new solutions are emerging. Smartphones now routinely demonstrate their potential as an interface of choice for operating complex, instrumented Lab-on-Chips. The sporadic nature of home-based in-vitro medical diagnostics testing calls for the development of systems capable of evolving with new applications or new technologies for Lab-on-Chip devices. We present in this work how we evolved the first generation of a smartphone/Lab-on-Chip platform designed for evolvability. We demonstrate how reengineering efforts can be confined to the mobile-software layer and illustrate some of the benefits of building evolvable systems. We implement electrochemical capabilities on our platform prototype and carry out cyclic voltammetry to measure dopamine concentrations over several orders of magnitude.

Micro- and nanoelectromechanical systems (MEMS/NEMS) have a high potential for mass sensing application. By miniaturization of the dimensions, higher and higher sensitivities can be achieved. Here we are presenting finite element modelling and optimization of a free-free beam type mechanical resonator. The hope is to optimize the mass sensitivity by increasing the Q-factor, which in turn, decreases the frequency noise in the system. Furthermore, a novel process sequence will be presented in order to fabricate micro and nanomechanical resonators with integrated electrostatic actuation and piezoresistive readout. Finally, some preliminary characterization results have been performed, demonstrating Q-factors up to 38,000in high vacuum and 13,000 at moderate vacuum, on an array of cantilever devices, giving us some insight on how to optimize the mechanical design for gas based measurements.

Unprecedented knowledge levels in life sciences along with technological advances in micro- and nanotechnologies and microfluidics have recently conditioned the advent of Lab-on-Chip (LoC) devices for In-Vitro Medical Testing(IVMT). Combined with smart-mobile technologies, LoCs are pervasively giving rise to opportunities to better diagnose disease, predict and monitor personalised treatment efficacy, or provide healthcare decision-making support at the Point-of-Care (PoC). Although made increasingly available to the consumer market, the adoption of LoC-based PoC In-Vitro Medical Testing (IVMT) systems is still in its infancy. This attrition partly pertains to the intricacy of designing and developing complex systems, destined to be used sporadically, in a fast-pace evolving technological paradigm. System evolvability is therefore key in the design process and constitutes the main motivation for this work.We introduce a smart-mobile and LoC-based system architecture designed for evolvability. By propagating LoC programmability, instrumentation, and control tools to the highlevel abstraction smart-mobile software layer, our architecturefacilitates the realisation of new use-cases and the accommodation for incremental LoC-technology developments. We demonstrate these features with an implementation allowing the interfacing of LoCs embedding current- or impedance-based biosensors such as Silicon Nanowire Field Effect Transistors(SiNW-FETs) or electrochemical transducers. Structural modifications of these LoCs or changes in their specific operation may be addressed by the sole reengineering of the mobilesoftware layer, minimising system upgrade development and validation costs and efforts.

Nanoparticles based on non-pathogenic viruses have opened up a novel sector in nanotechnology. Viral nanoparticles based on plant viruses have clear advantages over any synthetic nanoparticles as they are biocompatible and biodegradable self-assembled and can be produced inexpensively on a large scale. From several such under-development platforms, only a few have been characterized in the target-specific drugs into the cells. Potato virus X is presented as a carrier of the chemotherapeutic drug Herceptin that is currently used as a targeted therapy in (HER2+) breast cancer patients. Here, we used nanoparticles formed from the potato virus X to conjugate the Herceptin (Trastuzumab) monoclonal antibody as a new option in specific targeting of breast cancer. Bioconjugation was performed by EDC/sulfo-N-hydroxysuccinimide (sulfo-NHS) in a two-step protocol. Then, the efficiency of conjugation was investigated by different methods, including sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), Western blot, ELISA, Zetasizer, and transmission electron microscopy. SDS-PAGE and Western blot analysis confirmed an 82-kDa protein band that resulted from conjugation of potato virus X (PVX) coat protein (27 kDa) to heavy chain of Herceptin (55 kDa). Zeta potential values for conjugated particles, PVX, and HER were -7.05, -21.4, and -1.48, respectively. We investigated the efficiency of PVX-Herceptin to induce SK-OV-3 and SK-BR-3 cells (HER2 positive cell lines) apoptosis. We therefore counted cells and measured apoptosis by flow cytometry assay, then compared with Herceptin alone. Based on our data, we confirmed the conjugation of PVX and Herceptin. This study suggests that the PVX-Herceptin conjugates enable Herceptin to become more potential therapeutic tools.

Here we present a robust, stable and low-noise experimental set-up for performing electrochemical detection on a centrifugal microfluidic platform. By using a low-noise electronic component (electrical slip-ring) it is possible to achieve continuous, on-line monitoring of electrochemical experiments, even when the microfluidic disc is spinning at high velocities. Automated sample handling is achieved by designing a microfluidic system to release analyte sequentially, utilizing on-disc passive valving. In addition, the microfluidic system is designed to trap and keep the liquid sample stationary during analysis. In this way it is possible to perform cyclic voltammetry (CV) measurements at varying spin speeds, without altering the electrochemical response. This greatly simplifies the interpretation and quantification of data. Finally, real-time and continuous monitoring of an entire electrochemical experiment, including all intermediate sample handling steps, is demonstrated by amperometric detection of on-disc mixing of analytes (PBS and ferricyanide).

The resonance frequency and the Q-factor of the fundamental and higher order flexural modes of silicon dioxide microcantilevers have been characterized at different pressures and for different thicknesses of gold coating. We present the experimental results and discuss the effect of the gold film on the performance and sensitivity of the cantilevers when used as mass sensors. An almost linear relationship between the Q-factor and the resonance frequency of the uncoated cantilevers is observed, implying that a higher sensitivity can be attained by actuation at higher order resonant modes. We also find that even a thin gold coating may reduce Q-factors by more than an order of magnitude.

The resonance frequency of the fundamental and four higher order modes of a silicon dioxide microcantilever is measured. The effect on these modes of depositing a 400 nm gold coating is investigated theoretically and experimentally. We derive an analytical solution to the eigenmodes of a multi-layered cantilever and verify its validity by comparison to finite-element analysis as well as the experimentally obtained results. The temperature and pressure dependence of the resonance frequencies is investigated experimentally and found to be in good agreement with theoretical models. An experimentally obtained value for the temperature dependence of Young's modulus of elasticity for thermally grown SiO2 is presented.

We describe and demonstrate a two-volume collective scattering system for localized measurements of plasma turbulence. The finite crossfield correlation length of plasma turbulence combined with spatial variations in the magnetic field direction are used to obtain spatially localized turbulence measurements at the Wendelstein 7-AS fusion experiment. By comparing with localized measurements obtained using the single wide beam technique [Truc , Rev. Sci. Instrum. 63, 3716 (1992)] we provide a proof-of-principle demonstration of the two-beam method. An optimized configuration with large toroidal separation of the measurement volumes is predicted to be capable of providing spatial resolution better than 5 cm. (C) 2001 American Institute of Physics.

It has been speculated that the initial bending of cantilevers has a major influence on the detector signal in a cantilever-based sensor using the optical lever readout method. We have investigated theoretically as well as experimentally the changes induced in the detector signal when the optical lever technique is used to monitor a cantilever with initial bending during changes in the refractive index of the surrounding media. We find that for changes in refractive index as small as 10(-4) the detector signal is highly dependent on the initial bending of the cantilever. The findings are validated experimentally using an environmental chamber and varying the pressure. We sketch routes to circumvent the problem and formulas suitable for data treatment are given.

The ever-increasing complexity of the fabrication process of Point-of-care (POC) devices, due to high demand of functional versatility, compact size and ease-of-use, emphasizes the need of multifunctional materials that can be used to simplify this process. Polymers, currently in use for the fabrication of the often needed microfluidic channels, have limitations in terms of their physicochemical properties. Therefore, the use of a multipurpose biocompatible material with better resistance to the chemical, thermal and electrical environment, along with capability of forming closed channel microfluidics is inevitable. This paper demonstrates a novel technique of fabricating microfluidic devices using polyimide (PI) which fulfills the aforementioned properties criteria. A fabrication process to pattern microfluidic channels, using partially cured PI, has been developed by using a dry etching method. The etching parameters are optimized and compared to those used for fully cured PI. Moreover, the formation of closed microfluidic channel on wafer level by bonding two partially cured PI layers or a partially cured PI to glass with high bond strength has been demonstrated. The reproducibility in uniformity of PI is also compared to the most commonly used SU8 polymer, which is a near UV sensitive epoxy resin. The potential applications of PI processing are POC and biosensor devices integrated with microelectronics.

By positioning a single gold-particle at different locations along the length axis on a cantilever based mass sensor, we have investigated the effect of mass position on the mass responsivity and compared the results to simulations. A significant improvement in quality factor and responsivity was achieved by operating the cantilever in the 4/sup th/ bending mode, thereby increasing the intrinsic sensitivity. It is shown that the use of higher bending modes grants a spatial resolution and thereby enhances the functionality of the cantilever based mass sensor.

We present a system for characterization of the resonant properties of micro- and nanocantilever sensors. The system has been constructed as a vacuum chamber with capabilities for controlling environmental conditions such as pressure, temperature, and chemical constituents. Characterization can be achieved either electrically or using a specialized laser-optical detection system. The system has been used to characterize the resonant properties of SiO2 cantilevers as well as other resonant structures. We present experimental results of a SiO2 resonant cantilever, showing an exceptional accuracy in resonant frequency determination, and demonstrating the importance of resonance characterization in a controlled environment. ©2005 American Institute of Physics

The material properties of silicon rich nitride thin films are presented. Waveguides have been processed with this material as a core layer using LPCVD. The optical loss has been measured in straight waveguides of varying thickness.

The angular distribution of laser ablated silver has been measured in situ with a newly constructed setup with an array of microbalances. The distribution is strongly peaked in the forward direction corresponding to cospθ, where p varies between 5 and 9 for laser fluences from 2 to 7 J/cm2 at 355 nm for a beam spot of 0.015 cm2. The total deposited yield is of the order 1015 Ag-atoms per pulse.

By positioning a single gold particle at different locations along the length axis on a cantilever based mass sensor, we have investigated the effect of mass position on the mass responsivity and compared the results to simulations. A significant improvement in quality factor and responsivity was achieved by operating the cantilever in the fourth bending mode thereby increasing the intrinsic sensitivity. It is shown that the use of higher bending modes grants a spatial resolution and thereby enhances the functionality of the cantilever based mass sensor. (c) 2005 American Institute of Physics.

Recent advances within the realization of silica-based planar waveguide circuitry are presented. This ranges from the production methods for planar waveguides, including a novel method based on the utilization of focused UV-laser beams for direct waveguide imprinting, to the functionalities that are embedded into the glass materials and wave- guide circuitry. Planar waveguide amplifiers, lasers, and the pursuit to obtain highly nonlinear materials to realize purely glass-based switches, modulators, and wavelength converters are also presented. Further- more, microring resonators are discussed, and finally the latest results

Nanoresonator systems have been fully integrated on pre-processed complementary metal oxide semiconductor (CMOS) chips. The systems have been used for high sensitivity mass sensing in air and vacuum. The resonator system, which consists of a cantilever and structures for electrostatic actuation and capacitive read-out, has been defined by low energy electron beam lithography (EBL) combined with direct write laser lithography (DWL) on top of a radiation sensitive CMOS layer. The fabrication of the nanoresonator system has been conducted as a post-process step. CMOS integration radically decreases the parasitic capacitance, enabling detection and amplification of the resonance signal directly on the chip. Fabricated resonator systems have been designed to have resonance frequencies in the range of 1-1.6 MHz. A mass resolution of 3 ag/Hz has been determined in air by placing a single glycerine drop at the apex of a cantilever and subsequently measuring a frequency shift of 14.8 kHz. The frequency shift corresponds to an added mass of 50 fg, which is close to the estimated weight of 41 fg for the glycerine drop.

Amorphous silicon rich silicon nitride optical waveguides clad in silica are presented as a high-index contrast platform for high-density integrated optics. Performance of different cross-sectional geometries have been measured and are presented with regards to bending loss and insertion loss. A sample double ring add-drop filter is presented.

The optical nonlinearities of amorphous silicon rich nitride corresponding to χ(3) in a static electric field have been measured by tracking wavelength shifts in the resonances of optical waveguide ring resonators as a function of an applied electrical field. The magnitude of the nonlinearity measured agrees well with expected values.