cyc-DEP: Cyclic immunofluorescence profiling of particles collected using dielectrophoresis

Cancer is a highly heterogenous disease that requires precise detection tools and active surveillance methods. Liquid biopsy assays provide an agnostic way to follow the complex trajectory of cancer, providing better patient stratification tools for optimized treatment. Here, we present the development of a low-volume liquid biopsy assay called cyc-DEP (cyclic immunofluorescent imaging on dielectrophoretic chip) to profile biomarkers collected on a dielectrophoretic microfluidic chip platform. To enable on-chip cyclic imaging, we optimized a fluorophore quenching method and sequential rounds of on-chip staining with fluorescently conjugated primary antibodies. cyc-DEP allows for the quantification of a multiplex array of proteins using 25 µl of a patient plasma sample. We utilized nanoparticles from a prostate adenocarcinoma (LNCaP) cell line and a panel of six target proteins to develop our proof-of-concept technique. We then used cyc-DEP to quantify blood plasma levels of target proteins from healthy individuals, low-grade and high-grade prostate cancer patients (n = 3 each) in order to demonstrate that our platform is suitable for liquid biopsy analysis in its present form. To ensure accurate quantification of signal intensities and comparisons between different samples, we incorporated a signal intensity normalization method (fluorescent beads) and a custom signal intensity quantification algorithm that account for the distribution of signal across hundreds of collection regions on each chip. Our technique enabled a threefold improvement in multiplicity for detecting proteins associated with fluid samples, opening doors for early detection, and active surveillance through quantification of a multiplex array of biomarkers from low-volume liquid biopsies.     

Metal Enhanced Electrochemical Cyclooxygenase‐2 (COX‐2) Sensor for Biological Applications

Pain measurement is commonly required in biomedical and other emergency situations, yet there has been no pain biosensor reported in literature. Conventional approaches for pain measurement relies on Wong‐Baker face diagrams, which are grossly inadequate for situations involving children or unconscious people. We report a label‐free immunosensor for monitoring the pain biomarker cylooxygenase‐2 (COX‐2) in blood. The sensor is based on the concept of metal‐enhanced detection (MED). MED relies on the idea that the immobilization of underpotential deposition (upd) metallic films deposited either as a monolayer or electrostatically held onto a solid gold substrate could significantly amplify bimolecular recognition such as involving antigen‐antibody (Ab‐Ag) interactions. The surface bound Ab‐Ag complex insulates the electrode; causing a decrease in concentration‐dependent redox signals. A linear detection range of (3.64–3640.00)×10^?4 ng/mL was recorded with a detection limit of 0.25×10^?4 ng/mL, which was 4 orders of magnitude lower than that reported for ELISA for the same biomarker. The immunosensor exhibited selectivity of less than 6 % for potential interferents.     

Investigation of a UV-laser generated waveguide in a planar polymer chip using an improved interferometric method

Polymeric integrated-optical waveguides are prepared in a planar polymer chip by UV-laser lithographic methods. The waveguide samples are irradiated by an excimer laser at a wavelength Λ=248 nm with various irradiation parameters (different fluencies and irradiation doses). Mach-Zehnder interferometer is employed and the refractive index depth profiles of the waveguide samples are obtained. This profile covers two regions having exponential and Gaussian shapes. The model field distributions strongly depend on the refractive index of each region. The mode field distribution and the effective mode indices for each region have been calculated on the basis of a theoretical model and the experimentally measured data.     

The electrochemistry of antibody-modified conducting polymer electrodes

The modification of conducting polymer electrodes with antibodies (i.e. proteins) by means of electrochemical polymerization is a simple step that can be used to develop an immunological sensor. However, the electrochemical processes involved leading to the generation of analytical signals by the sensor have not been fully investigated. In this work, we report on the characterization of the interaction between an antigen, human serum albumin (HSA) and an antibody-immobilized polypyrrole electrode (such as anti-HSA) using cyclic voltammetry (CV) and impedance spectroscopy. This interaction was monitored using electrochemical impedance spectroscopy at three different potentials. The potentials correspond to the three redox states of the electroconducting polymer (i.e. reduced, doped and overoxidized states). Evidence from the CV experiments confirmed that there was a shift in the potential, which was found to be proportional to the concentration. Both the CV and the impedance experiments indicated that this potential-dependent shift could be attributed to antibody–antigen (Ab–Ag) binding.     

RF-sputtered CrB2 diffusion barrier for Ni/Au Ohmic contacts on p-CuCrO2

Ohmic contacts to p-type CuCrO₂ using Ni/Au/CrB₂/Ti/Au contact metallurgy are reported. The samples were annealed in the 200–700 °C range for 60 s in flowing oxygen ambient. A minimum specific contact resistance of 2 × 10⁻⁵ Ω cm² was obtained after annealing at 400 °C. Further increase in the annealing temperature (>400 °C) resulted in the degradation of contact resistance. Auger Electron Spectroscopy (AES) depth profiling showed that out-diffusion of Ti to the surface of the contact stacks was evident by 400 °C, followed by Cr at higher temperature. The CrB₂ diffusion barrier decreases the specific contact resistance by almost two orders of magnitude relative to Ni/Au alone.     

Computer simulations of astronomical objects as seen by ground based optical telescopes

Computer simulations were carried out to investigate the limitations imposed by atmospheric turbulence on observing astronomical objects by 3·5 and 1·25 m optical telescopes. These limitations were studied in terms of the modulation transfer function of a reference star and the autocorrelation function of a binary star. Results demonstrate the quantitative comparative study between these telescopes in the presence of different seeing conditions for both short- and long-exposure recording.     

Forced convection from a microstructure on a flat plate

In this work, a cooling of a flat microelectronic structure with single-phase forced convection is investigated. The axial conduction, usually neglected in boundary layer theory, is considered here since the length of the heated element is in the same order of magnitude as the thickness of the boundary layer. The microstructure represents a package of chips mounted flush with the surface of the plate, and uniformly heated with a constant heat flux. The differential method is used to reduce the governing partial differential equations to ordinary differential ones, which are solved numerically by the use of a computational code developed by the authors. This code is based on Keller–Box method. The temperature profiles and Nusselt numbers are plotted at several locations on the heated element and are given as functions of the Reynolds number at the beginning of heated microstructure and of the ratio of unheated to heated length. Furthermore, the average Nusselt numbers on the heated length are computed for Prandtl numbers in the range 0.7≤Pr≤7,000. The results are compared to the boundary layer solution of unheated starting length problem. The results will be used as a baseline for successively more complex situations of cooling in electronics.     

Plasma-based preparation of polyaniline/graphene and polypyrrole/graphene composites for dye-sensitized solar cells as counter electrodes

This study presents the preparation of graphene (GR) nanocomposites with polyaniline (PANI) and polypyrrole (PPy) through the fast, versatile and environmentally friendly process of radio frequency (RF)-plasma polymerization. Morphological characterization of the nanocomposites is performed using scanning electron microscopy (SEM) and shows that the PANI and PPy conducting polymers coated the GR surface. The surface properties of the GR nanocomposites are determined using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). The prepared GR nanocomposites are then used as counter electrodes in dye-sensitized solar cells (DSSCs). The conversion cell efficiencies for iodine-doped DSSC samples are found to be 0.086%, 5.41%, and 5.60% for I₂-PANI, I₂-PANI-GR and I₂-PPy-GR, respectively, while the corresponding undoped samples reaches power conversion efficiencies of 3.82%, 1.30%, and 0.077% for PPy-GR, PANI-GR and PANI, respectively. The incident photon-to-current efficiency (IPCE) of iodine-doped composite-based DSSCs is significantly enhanced.     

Extremal Problems in the Class of Delta-Subharmonic Functions of Finite Order in a Half-Plane

We obtain exact lower bounds of the upper limits of ratios of the Nevanlinna characteristics of a delta-subharmonic function in the upper half-plane.     

Design trade-offs in optoelectronic parallel processing systems using smart-SLMs

Optoelectronic devices with free-space optical interconnections offer new possibilities in massively parallel processing. The trade-offs involved in system design and device selection for optoelectronic implementations are examined. System design trade-offs are approached from algorithmic and technological standpoints. From the algorithmic standpoint, new architectures based on expander graphs, that have been shown to provide low-contention fault-tolerant communication, are discussed. Optoelectronic systems which implement such random graphs can be folded to reduce the hardware cost or unfolded to increase bandwidth. They can also be partially folded by increasing the grain size or by reducing the randomness of the graph topology to reduce the complexity of the interconnection holograms. An optoelectronic and a VLSI implementation of a multistage interconnection network are compared from a technological standpoint. Physical design parameters, such as the chip size or the number of phase levels of the interconnection holograms, are related to the system design metrics such as bandwidth, volume, area and power. It is shown that the optoelectronic implementations have higher performance and are more cost-effective than VLSI implementations. These results are also used to provide general guidelines for device selection in the design of smart pixels/smart spatial light modulators based optoelectronic systems.