Integrated membrane-free thermal flow sensor for silicon-on-glass microfluidics.

Lab-on-a-chip (LOC) forms the basis of new-generation portable analytical systems. LOC allows the manipulation of ultralow flows of liquid reagents and multistep reactions on a microfluidic chip, which requires a robust and precise instrument to control the flow of liquids on a chip. However, commercially available flow meters appear to be a standalone option adding a significant dead volume of tubes for connection to the chip. Furthermore, most of them cannot be fabricated within the same technological cycle as microfluidic channels. Here, we report on a membrane-free microfluidic thermal flow sensor (MTFS) that can be integrated into a silicon-glass microfluidic chip with a microchannel topology. We propose a membrane-free design with thin-film thermo-resistive sensitive elements isolated from microfluidic channels and a 4'' wafer silicon-glass fabrication route. It ensures MTFS compatibility with corrosive liquids, which is critically important for biological applications. MTFS design rules for the best sensitivity and measurement range are proposed. A method for automated thermo-resistive sensitive element calibration is described. The device parameters are experimentally tested for hundreds of hours with a reference Coriolis flow sensor demonstrating a relative flow error of less than 5% within the range of 2-30 µL min-1 along with a sub-second time response.

Low-loss silicon nitride photonic ICs for near-infrared wavelength bandwidth.

Low-loss photonic integrated circuits (PICs) are the key elements in future quantum technologies, nonlinear photonics and neural networks. The low-loss photonic circuits technology targeting C-band application is well established across multi-project wafer (MPW) fabs, whereas near-infrared (NIR) PICs suitable for the state-of-the-art single-photon sources are still underdeveloped. Here, we report the labs-scale process optimization and optical characterization of low-loss tunable photonic integrated circuits for single-photon applications. We demonstrate the lowest propagation losses to the date (as low as 0.55 dB/cm at 925 nm wavelength) in single-mode silicon nitride submicron waveguides (220×550 nm). This performance is achieved due to advanced e-beam lithography and inductively coupled plasma reactive ion etching steps which yields waveguides vertical sidewalls with down to 0.85 nm sidewall roughness. These results provide a chip-scale low-loss PIC platform that could be even further improved with high quality SiO2 cladding, chemical-mechanical polishing and multistep annealing for extra-strict single-photon applications.

Human Angiotensin I-Converting Enzyme Produced by Different Cells: Classification of the SERS Spectra with Linear Discriminant Analysis.

Angiotensin I-converting enzyme (ACE) is a peptidase widely presented in human tissues and biological fluids. ACE is a glycoprotein containing 17 potential N-glycosylation sites which can be glycosylated in different ways due to post-translational modification of the protein in different cells. For the first time, surface-enhanced Raman scattering (SERS) spectra of human ACE from lungs, mainly produced by endothelial cells, ACE from heart, produced by endothelial heart cells and miofibroblasts, and ACE from seminal fluid, produced by epithelial cells, have been compared with full assignment. The ability to separate ACEs' SERS spectra was demonstrated using the linear discriminant analysis (LDA) method with high accuracy. The intervals in the spectra with maximum contributions of the spectral features were determined and their contribution to the spectrum of each separate ACE was evaluated. Near 25 spectral features forming three intervals were enough for successful separation of the spectra of different ACEs. However, more spectral information could be obtained from analysis of 50 spectral features. Band assignment showed that several features did not correlate with band assignments to amino acids or peptides, which indicated the carbohydrate contribution to the final spectra. Analysis of SERS spectra could be beneficial for the detection of tissue-specific ACEs.

ITO film stack engineering for low-loss silicon optical modulators.

The Indium Tin Oxide (ITO) platform is one of the promising solutions for state-of-the-art integrated optical modulators towards low-loss silicon photonics applications. One of the key challenges on this way is to optimize ITO-based thin films stacks for electro-optic modulators with both high extinction ratio and low insertion loss. In this paper we demonstrate the e-beam evaporation technology of 20 nm-thick ITO films with low extinction coefficient of 0.14 (Nc = 3.7·1020 cm-3) at 1550 nm wavelength and wide range of carrier concentrations (from 1 to 10 × 1020 cm-3). We investigate ITO films with amorphous, heterogeneously crystalline, homogeneously crystalline with hidden coarse grains and pronounced coarsely crystalline structure to achieve the desired optical and electrical parameters. Here we report the mechanism of oxygen migration in ITO film crystallization based on observed morphological features under low-energy growth conditions. Finally, we experimentally compare the current-voltage and optical characteristics of three electro-optic active elements based on ITO film stacks and reach strong ITO dielectric permittivity variation induced by charge accumulation/depletion (Δn = 0.199, Δk = 0.240 at λ = 1550 nm under ± 16 V). Our simulations and experimental results demonstrate the unique potential to create integrated GHz-range electro-optical modulators with sub-dB losses.

Self-Controlled Cleaving Method for Silicon DRIE Process Cross-Section Characterization.

Advanced microsystems widely used in integrated optoelectronic devices, energy harvesting components, and microfluidic lab-on-chips require high-aspect silicon microstructures with a precisely controlled profile. Such microstructures can be fabricated using the Bosch process, which is a key process for the mass production of micro-electro-mechanical systems (MEMS) devices. One can measure the etching profile at a cross-section to characterize the Bosch process quality by cleaving the substrate into two pieces. However, the cleaving process of several neighboring deeply etched microstructures is a very challenging and uncontrollable task. The cleaving method affects both the cleaving efficiency and the metrology quality of the resulting etched microstructures. The standard cleaving technique using a diamond scriber does not solve this issue. Herein, we suggest a highly controllable cross-section cleaving method, which minimizes the effect on the resulting deep etching profile. We experimentally compare two cleaving methods based on various auxiliary microstructures: (1) etched transverse auxiliary lines of various widths (from 5 to 100 µm) and positions; and (2) etched dashed auxiliary lines. The interplay between the auxiliary lines and the etching process is analyzed for dense periodic and isolated trenches sized from 2 to 50 µm with an aspect ratio of more than 10. We experimentally showed that an incorrect choice of auxiliary line parameters leads to silicon "build-up" defects at target microstructures intersections, which significantly affects the cross-section profile metrology. Finally, we suggest a highly controllable defect-free cross-section cleaving method utilizing dashed auxiliary lines with the stress concentrators.

Cyclic on-chip bacteria separation and preconcentration.

Nanoparticles and biological molecules high throughput robust separation is of significant interest in many healthcare and nanoscience industrial applications. In this work, we report an on-chip automatic efficient separation and preconcentration method of dissimilar sized particles within a microfluidic platform using integrated membrane valves controlled microfiltration. Micro-sized E. coli bacteria are sorted from nanoparticles and preconcentrated on a microfluidic chip with six integrated pneumatic valves (sub-100 nL dead volume) using hydrophilic PVDF filter with 0.45 µm pore diameter. The proposed on-chip automatic sorting sequence includes a sample filtration, dead volume washout and retentate backflush in reverse flow. We showed that pulse backflush mode and volume control can dramatically increase microparticles sorting and preconcentration efficiency. We demonstrate that at the optimal pulse backflush regime a separation efficiency of E. coli cells up to 81.33% at a separation throughput of 120.45 µL/min can be achieved. A trimmed mode when the backflush volume is twice smaller than the initial sample results in a preconcentration efficiency of E. coli cells up to 121.96% at a throughput of 80.93 µL/min. Finally, we propose a cyclic on-chip preconcentration method which demonstrates E. coli cells preconcentration efficiency of 536% at a throughput of 1.98 µL/min and 294% preconcentration efficiency at a 10.9 µL/min throughput.

Multiscale flaked silver SERS-substrate for glycated human albumin biosensing.

Original multiscale flaked silver SERS-substrate (MFSS substrate) was applied for glycated albumin (GA) biosensing. The substrate is composed from silver flakes that have three orders of magnitude size dispersion: from 50 nm to 2 µm. The multiscale silver structure refracts the incident light and various surface plasmons are excited. Some of the internal plasmons are localized and give rise of the large local electric field. It was demonstrated that Raman scattering signal strongly depends: a) on "hot spots" formation at the edges and points of contact of silver plates, and b) on the angle of incidence. As a result the silver structure operates as an effective SERS substrate. To achieve the selectivity to glycated part, the surface of SERS-substrate was modified with 4-mercaptophenylboronic acid (4-mPBA). Various saccharides (Fru, Glc, Suc, Dex) were taken as model compounds for the glycated proteins determination. The saccharides contain cis-diol groups that form five- or six-membered ethers with boronic acid. Spectrum of SERS-substrate changes after sugar/glycated albumin treatment. Main differences in the SERS-spectra of sugar/glycated albumin treated SERS-substrate and control are referred to phenylboronic acid vibrations (999, 1021, 1072 and 1589 cm-1). Principal component analysis (PCA) and Partial Least Squares Regression (PLS-R) were used to discriminate spectra and to construct calibration curve, as well as to measure GA values in real samples of human plasma. Multiscale flaked silver SERS-substrate modified with 4-mPBA allows quantitative one-step biosensing of glycated albumin in 15 µl of human plasma.

Quantum Engineering of Atomically Smooth Single-Crystalline Silver Films.

There is a demand for ultra low-loss metal films with high-quality single crystals and perfect surface for nanophotonics and quantum information processing. Many researches are devoted to alternative materials, but silver is by far theoretically the most preferred low-loss material at optical and near-IR frequencies. Usually, epitaxial growth is used to deposit single-crystalline silver films, but they still suffer from unpredictable losses and well-known dewetting effect that strongly limits films quality. Here we report the two-step approach for e-beam evaporation of atomically smooth single-crystalline metal films. The proposed method is based on the thermodynamic control of film growth kinetics at atomic level, which allows depositing state-of-art metal films and overcoming the film-surface dewetting. Here we use it to deposit 35-100 nm thick single-crystalline silver films with the sub-100pm surface roughness and theoretically limited optical losses, considering an ideal material for ultrahigh-Q nanophotonic devices. Utilizing these films we experimentally estimate the contribution of grain boundaries, material purity, surface roughness and crystallinity to optical properties of metal films. We demonstrate our «SCULL¼ two-step approach for single-crystalline growth of silver, gold and aluminum films which open fundamentally new possibilities in nanophotonics, biotechnology and superconductive quantum technologies. We believe it could be readily adopted for the synthesis of other extremely low-loss single-crystalline metal films.

Ultrabright Room-Temperature Sub-Nanosecond Emission from Single Nitrogen-Vacancy Centers Coupled to Nanopatch Antennas.

Solid-state quantum emitters are in high demand for emerging technologies such as advanced sensing and quantum information processing. Generally, these emitters are not sufficiently bright for practical applications, and a promising solution consists in coupling them to plasmonic nanostructures. Plasmonic nanostructures support broadband modes, making it possible to speed up the fluorescence emission in room-temperature emitters by several orders of magnitude. However, one has not yet achieved such a fluorescence lifetime shortening without a substantial loss in emission efficiency, largely because of strong absorption in metals and emitter bleaching. Here, we demonstrate ultrabright single-photon emission from photostable nitrogen-vacancy (NV) centers in nanodiamonds coupled to plasmonic nanocavities made of low-loss single-crystalline silver. We observe a 70-fold difference between the average fluorescence lifetimes and a 90-fold increase in the average detected saturated intensity. The nanocavity-coupled NVs produce up to 35 million photon counts per second, several times more than the previously reported rates from room-temperature quantum emitters.

Light localization and SERS in tip-shaped silicon metasurface.

Optical properties of two dimensional periodic system of the silicon micro-cones are investigated. The metasurface, composed of the silicon tips, shows enhancement of the local optical field. Finite element computer simulations as well as real experiment reveal anomalous optical response of the dielectric metasurface due to excitation of the dielectric resonances. Various electromagnetic resonances are considered in the dielectric cone. The metal-dielectric resonances, which are excited between metal nanoparticles and dielectric cones, are also considered. The resonance local electric field can be much larger than the field in the usual surface plasmon resonances. To investigate local electric field the signal molecules are deposited on the metal nanoparticles. We demonstrate enhancement of the electromagnetic field and Raman signal from the complex of DTNB acid molecules and gold nanoparticles, which are distributed over the metasurface. The metasurfaces composed from the dielectric resonators can have quasi-continuous spectrum and serve as an efficient SERS substrates.

SERS-active dielectric metamaterials based on periodic nanostructures.

New dielectric SERS metamaterial is investigated. The material consists of periodic dielectric bars deposited on the metal substrate. Computer simulations as well as real experiment reveal extraordinary optical reflectance in the proposed metamaterial due to the excitation of the multiple dielectric resonances. We demonstrate the enhancement of the Raman signal from the complex of 5,5'-dithio-bis-[2-nitrobenzoic acid] molecules and gold nanoparticle (DTNB-Au-NP), which is immobilized on the surface of the barshaped dielectric metamaterial.