This PDF file contains the front matter associated with SPIE Proceedings Volume 10247, including the Title Page, Copyright information, Table of Contents, Introduction (if any), and Conference Committee listing.

In this paper, a study of the power loss attenuation of the plane wave travelling through the tissue layers, from the outside to the inside of the skull within a cochlear implant, is performed. Different implantation depths of the internal antenna from 10 to 30 mm are considered. To this purpose, the gain and attenuation in dB are studied. A multilayer tissue model is developed, consisting of mainly skin, mastoid bone and brain. An s-parameter analysis is also carried out, using loop antennas and simulated head tissue. Ansoft Ansys® HFSS software is used for electro-magnetic simulations of the antennas, placed in different types of human tissues. Smith charts for antenna placed in both skin and multi-tissue model are included.

The deadliest disease in the world is coronary artery disease (CAD), which is related to a narrowing (stenosis) of blood vessels due to fatty deposits, plaque, on the arterial walls. The level of stenosis in the coronary arteries can be assessed by Fractional Flow Reserve (FFR) measurements. This involves determining the ratio between the maximum achievable blood flow in a diseased coronary artery and the theoretical maximum flow in a normal coronary artery. The blood flow is represented by a pressure drop, thus a pressure wire or pressure sensor integrated in a catheter can be used to calculate the ratio between the coronary pressure distal to the stenosis and the normal coronary pressure. A 2 Fr (0.67mm) outer diameter catheter was used, which required a high level of microelectronics miniaturisation to fit a pressure sensing system into the outer wall. The catheter has an eccentric guidewire lumen with a diameter of 0.43mm, which implies that the thickest catheter wall section provides less than 210 microns height for flex assembly integration consisting of two dies, a capacitive MEMS pressure sensor and an ASIC. In order to achieve this a very thin circuit flex was used, and the two chips were thinned down to 75 microns and flip chip mounted face down on the flex. Many challenges were involved in obtaining a flex layout that could wrap into a small tube without getting the dies damaged, while still maintaining enough flexibility for the catheter to navigate the arterial system.

This paper reports on a microfluidic platform with an integrated spin valve giant magneto-resistance (GMR) sensor used for the detection and quantification of single magnetic micromarkers. A microfluidic channel containing the magnetic fluid, microconductors (MCs) for collection of the magnetic markers and a spin valve GMR sensor for detecting the presence of their magnetic stray field were integrated on a single chip. The results show that the sensor is capable of detecting a single magnetic marker with 2.8 μm diameter.

We present a microfluidic chip for an easy setup of a 3D-culture of mammalian cells. The chip contains feeding structures and gas supply for long-term cultivation of mammalian cells. The device is fabricated out of hard materials like silicon and glass that are all highly biocompatible. The chip uses the concept of surficial phaseguides that allows the partial filling of a microfluidic chip with liquids based on hydrophobic and hydrophilic surfaces. Here, a suspension of mammalian cells and melted agarose is filled into the chip and is pulled by the capillary pressure on the hydrophilic areas but not on the hydrophobic phaseguides. Consequently, only a part of the chip is filled with the agarose which gels by cooling a form the 3D-cell culture. The unfilled areas are used as supply structures for nutrition and gases. So the supply is based on diffusion and the supply of nutrition and gases is controlled independently. We cultured HaCaT-cells over 24 hours in our device and achieve a good viability.

An additive manufacturing concept, consisting of 3D photopolymer printing and Ag nanoparticle printing, was investigated for the construction of a microfluidic biosensor based on immobilized cytochrome P450 enzyme. An acylate-type microfluidic chamber composed of two parts, i.e. chamber-housing and chamber-lid was printed with a polyjet 3D printer. A 3-electrode sensor structure was inkjet-printed on the lid using a combination of Ag and graphene printing. The working electrode was covered with carbon nanotubes by drop-casting and immobilized with cytochrome P450 2D6 enzyme. The microfluidic sensor shows a significant response to a test xenobiotic, i.e. dextromethorphan; the cyclic voltammetrical measurements show a corresponding oxidation peak at 0.4 V with around 5 μM detection limit.

This paper reports a low area, low power, integer-based digital processor for the calculation of phase synchronization between two neural signals. The processor calculates the phase-frequency content of a signal by identifying the specific time periods associated with two consecutive minima. The simplicity of this phase-frequency content identifier allows for the digital processor to utilize only basic digital blocks, such as registers, counters, adders and subtractors, without incorporating any complex multiplication and or division algorithms. In fact, the processor, fabricated in a 0.18μm CMOS process, only occupies an area of 0.0625μm² and consumes 12.5nW from a 1.2V supply voltage when operated at 128kHz. These low-area, low-power features make the proposed processor a valuable computing element in closed loop neural prosthesis for the treatment of neural diseases, such as epilepsy, or for extracting functional connectivity maps between different recording sites in the brain.

In this paper, a high-resolution bio-optical sensor is developed for brain activity measurement. The aim is to develop an optical sensor with enough sensitivity to detect small electric field perturbations caused by neuronal action potential. The sensing element is a polymeric dielectric micro-resonator fabricated in a spherical shape with a few hundred microns in diameter. They are made of optical quality polymers that are soft which make them mechanically compatible with tissue. The sensors are attached to or embedded in optical fibers which serve as input/output conduits for the sensors. Hundreds or even thousands of spheres can be attached to a single fiber to detect and transmit signals at different locations. The high quality factor for the optical resonator makes it significantly used in such bio-medical applications. The sensing phenomenon is based on whispering gallery modes (WGM) shifts of the optical sensor. To mimic the brain signals, the spherical resonator is immersed in a homogeneous electrical field that is created by applying potential difference across two metallic plates. One of the plates has a variable voltage while the volt on the other plate kept fixed. Any small perturbations of the potential difference (voltage) lead to change in the electric field intensity. In turn the sensor morphology will be affected due to the change in the electrostriction force acting on it causing change in its WGM. By tracking these WGM shift on the transmission spectrum, the induced potential difference (voltage change) could be measured. Results of a mathematical model simulation agree well with the preliminary experiments. Also, the results show that the brain activity could be measured using this principle.

In this paper we demonstrate a dark field video imaging system for the detection and size characterization of individual magnetic micromarkers suspended in liquid and the detection of pathogens utilizing magnetically labelled E.coli. The system follows dynamic processes and interactions of moving micro/nano objects close to or below the optical resolution limit, and is especially suitable for small sample volumes (~ 10 μl). The developed detection method can be used to obtain clinical information about liquid contents when an additional biological protocol is provided, i.e., binding of microorganisms (e.g. E.coli) to specific magnetic markers. Some of the major advantages of our method are the increased sizing precision in the micro- and nano-range as well as the setup’s simplicity making it a perfect candidate for miniaturized devices. Measurements can thus be carried out in a quick, inexpensive, and compact manner. A minor limitation is that the concentration range of micromarkers in a liquid sample needs to be adjusted in such a manner that the number of individual particles in the microscope’s field of view is sufficient.

There remains a great need for diagnosis of inflammatory bowel disease (IBD), for which the current technique, colonoscopy, is not cost-effective and presents a non-negligible risk for complications. Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy is a new screening technique to evaluate colitis. Comparing infrared spectra of sera to study the differences between them can prove challenging due to the complexity of its biological constituents giving rise to a plethora of vibrational modes. Overcoming these inherent infrared spectral analysis difficulties involving highly overlapping absorbance peaks and the analysis of the data by curve fitting to improve the resolution is discussed. The proposed technique uses colitic and normal wild type mice dried serum to obtain ATR/FTIR spectra to effectively differentiate colitic mice from normal mice. Using this method, Amide I group frequency (specifically, alpha helix to beta sheet ratio of the protein secondary structure) was identified as disease associated spectral signature in addition to the previously reported glucose and mannose signatures in sera of chronic and acute mice models of colitis. Hence, this technique will be able to identify changes in the sera due to various diseases.

In this paper, we present a new fabrication method for the whispering gallery mode (WGM) micro-sphere based electric field sensor that which allows for longer time periods of sensitivity. Recently, a WGM-based photonic electric field sensor was proposed using a coupled dielectric microsphere-beam. The external electric field imposes an electrtrostriction force on the dielectric beam, deflecting it. The beam, in turn compresses the sphere causing a shift in its WGM. As part of the fabrication process, the PDMS micro-beams and the spheres are curied at high-temperature (100oC) and subsequently poled by exposing to strong external electric field (~8 MV/m) for two hours. The poling process allows for the deposition of surface charges thereby increasing the electrostriction effect. This methodology is called curing-then-poling (CTP). Although the sensors do become sufficiently sensitive to electric field, they start de-poling after a short period (within ~ 10 minutes) after poling, hence losing sensitivity. In an attempt to mitigate this problem and to lock the polarization for a longer period, we use an alternate methodology whereby the beam is poled and cured simultaneously (curing-while-poling or CWP). The new fabrication method allows for the retention of polarization (and hence, sensitivity to electric field) longer (~ 1500 minutes). An analysis is carried out along with preliminary experiments. Results show that electric fields as small as ~ 100 V/m can be detected with a 300 μm diameter sphere sensor a day after poling.

The paper presents the application of electrical impedance spectroscopy (EIS) analysis for investigation of cardiac cell (H9C2 – rat cardiomyoblast) proliferation after verapamil hydrochloride exposure. For this purpose, two different PDMS/glass microsystems with circular microchamber and longitudinal microchannel integrated with Pt/Al electrodes were used. The microchambers were fabricated in PDMS using photolithography and replica moulding techniques. Pt/Al electrodes were fabricated on a 4-inch glass substrate using Physical Vapor Deposition (PVD). Solution of verapamil hydrochloride was continuously introduced into the microsystems with H9C2 cell culture (a flow rate of 1 μl/min) for 72 h. The impedance spectra were recorded from 100 Hz to 1 MHz. We confirmed that impedance spectroscopy can be used for non-invasive, label-free and real-time analysis of cardiac cells proliferation based on cells dielectric properties and biological structure.

We propose the novel structure of an interferometric biosensor based on multimode interference (MMI) waveguides. We present the design of the biosensor using eigenmode expansion (EME) method in accordance with the requirements and standards of today's photonic technology. The MMI structures with a 90 nm Si₃N₄ core are used as power splitters with 5 outputs. The 5 high-resolution images at the end of the multimode region show high power balance. We analyze the coupling efficiency of the laser source with the structure, the excess loss and power imbalance for different compact MMI waveguides with widths ranging from 45 μm to 15 μm. For a laser source with a tolerance of ±1mm in linearization we could achieve a coupling efficiency of 52%. MMI waveguides with tapered channels show excess loss values under 0.5 dB and power imbalance values under 0.08 dB. In addition, we show that for a 10 nm deviation of the source wavelength from its optimal value and for a 10 μm deviation of the MMI length from its optimal value, the performance of the MMI waveguides remains acceptable. Finally, we analyze the power budget of the whole biosensor structure and show that it is sufficient for the proper operation of this device.

In this paper, a sensor system architecture for laboratory and in-vivo light scattering studies on blood cells is presented. It aims at correlating Mie scattering to compositional and physiological information of blood cells towards a non-invasive blood-cell counting sensor. An overview of previously reported experimental techniques on light scattering from blood cells is presented. State-of-the-art methods such as differential pulse measurements, vessel pressure optimization identified as promising for enhancing the scattering signal in such measurements. Indicative simulations of Mie scattering by blood cells are presented, illustrating the potential for distinguishing among cells and identifying size distribution. A prototype sensor system based on a 640-660 nm laser light source and a photo diode array is implemented and programmed to obtain mean amplitude and scattering angle measurements.

In this contribution, we present travelling-wave based dielectrophoretic (twDEP) microfluidic devices for the handling of suspended grown cells. Travelling-wave based dielectrophoretic devices rely on a moving electric field gradient, which can be realised by applying phase-shifted AC-voltages between sets of parallel electrodes. The distance between these electrodes can be reduced to a few micrometres. In optimised conditions, channels with a height of even hundreds of micrometres are applicable. Two microfluidic devices have been realised to investigate the advantages of travellingwave dielectrophoresis for cell handling.