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.     

Massively parallel low-cost pick-and-place of optoelectronic devices by electrochemical fluidic processing

We describe a novel electrochemical technique for the nonlithographic, fluidic pick-and-place assembly of optoelectronic devices by electrical and optical addressing. An electrochemical cell was developed that consists of indium tin oxide (ITO) and n -type silicon substrates as the two electrode materials and deionized water (R = 18 MOmega) as the electrolytic medium between the two electrodes. 0.8-20-microm-diameter negatively charged polystyrene beads, 50-100-microm-diameter SiO(2) pucks, and 50-microm LED's were successfully integrated upon a patterned silicon substrate by electrical addressing. In addition, 0.8-microm-diameter beads were integrated upon a homogeneous silicon substrate by optical addressing. This method can be applied to massively parallel assembly (>1000 x 1000 arrays) of multiple types of devices (of a wide size range) with very fast (a few seconds) and accurate positioning.     

Self-injection length in La0.7Ca0.3MnO3-YBa2Cu3O7-δ ferromagnet-superconductor multilayer thin films

We have carried out extensive studies on the self-injection problem in barrierless heterojunctions between La_0.7Ca_0.3MnO₃ (LCMO) and YBa₂Cu₃O_7-δ (YBCO) thin films. The heterojunctions were formed in situ by sequentially growing LCMO and YBCO films on 〈100〉 LaAlO₃ (LAO) substrate using a pulsed laser deposition (PLD) system. YBCO micro-bridges with 64 μm width were patterned both on the LAO (control) and LCMO side of the substrate. Critical current, I _c, was measured at 77 K on both the control side as well as the LCMO side for different YBCO film thickness. It was observed that while the control side showed a J _c of ∼ 2 × 10⁶ A/cm², the LCMO side showed about half the value for the same thickness (1800 ?). The difference in J _c indicates that a certain thickness of YBCO has become ‘effectively’ normal due to self-injection. From the measurement of J _c at two different thicknesses (1800 ? and 1500 ?) of YBCO films both on the LAO as well as the LCMO side, the value of self-injection length (at 77 K) was estimated to be ∼ 900 ?. To the authors’ best knowledge, this is the first time that self-injection length has been quantified. A control experiment carried out with LaNiO₃ deposited by PLD on YBCO did not show any evidence of self-injection.     

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.     

Investigation of the thermoelectrical properties of the Sn91.2−x–Zn8.8–Agx alloys

Journal of Thermal Analysis and Calorimetry - Sn91.2?x–Zn8.8–Agx alloys (x = 0.15–10.0 wt%) were directionally solidified upwards at a constant G...     

Extraction protocol and mass spectrometry method for quantification of doxorubicin released locally from prodrugs in tumor tissue

The localized conversion of inactive doxorubicin prodrug chemotherapeutics to pharmacalogically active forms is difficult to quantify in mouse tumor models because it occurs only in small regions of tissue. The tumor tissue extraction protocol and LC–MS/MS analysis method described here were optimized to obtain a detection limit of 7.8 pg for the activated doxorubicin and 0.36 ng for the doxorubicin prodrug. This method can be useful for determining the biodistribution and activation efficiency for many different doxorubicin prodrugs. It can also be used for quantification of doxorubicin from tumor models that have poor vascularization resulting in low tissue accumulation. Copyright © 2013 John Wiley & Sons, Ltd.     

Magnetoelectric effect in cobalt ferrite-barium titanate composites and their electrical properties

CoFe₂O₄-BaTiO₃ composites were prepared using conventional ceramic double sintering process with various compositions. Presence of two phases in the composites was confirmed using X-ray diffraction. The dc resistivity and thermoemf as a function of temperature in the temperature range 300 K to 600 K were measured. Variation of dielectric constant (ɛ′) with frequency in the range 100 Hz to 1 MHz and also with temperature at a fixed frequency of 1 kHz was studied. The ac conductivity was derived from dielectric constant (ɛ′) and loss tangent (tan δ). The nature of conduction is discussed on the basis of small polaron hopping model. The static value of magnetoelectric conversion factor has been studied as a function of magnetic field.     

Energy dependence of multiplicity in proton-nucleus collisions and models of multiparticle production

This is a continuation of our earlier investigation (Gurtuet al 1974Phys. Lett. 50 B 391) on multiparticle production in proton-nucleus collisions based on an exposure of emulsion stack to 200 GeV/c beam at the NAL. It is found that the ratioR _em = 〈n _s〉/〈n _ch〉, where 〈n _ch〉 is the charged particle multiplicity in pp-collisions, increases slowly from about 1 at 10 GeV/c to 1·6 at 68 GeV/c and attains a constant value of 1·71 ± 0·04 in the region 200 to 8000 GeV/c. Furthermore,R _em = 1·71 implies an effectiveA-dependence ofR _A =A ^0.18,i.e., a very weak dependence. Predictions ofR _em on various models are discussed and compared with the emulsion data. Data seem to favour models of hadron-nucleon collisions in which production of particles takes place through adouble step mechanism,e.g., diffractive excitation, hydrodynamical and energy flux cascade as opposed to models which envisage instantaneous production.