Enhancing Multichannel Laser-Doppler Vibrometry Signals with Application to (Carotid-Femoral) Pulse Transit Time Estimation.

Pulse-wave velocity (PWV) can be used to quantify arterial stiffness, allowing for a diagnosis of this condition. Multi-beam laser-doppler vibrometry offers a cheap, non-invasive and user-friendly alternative to measuring PWV, and its feasibility has been previously demonstrated in the H2020 project CARDIS. The two handpieces of the prototype CARDIS device measure skin displacement above main arteries at two different sites, yielding an estimate of the pulse-transit time (PTT) and, consequently, PWV. The presence of multiple beams (channels) on each handpiece can be used to enhance the underlying signal, improving the quality of the signal for PTT estimation and further analysis. We propose two methods for multi-channel LDV data processing: beamforming and beamforming-driven ICA. Beamforming is done by an SNR-weighted linear combination of the time-aligned channels, where the SNR is blindly estimated from the signal statistics. ICA uses the beamformer to resolve its inherent permutation and scale ambiguities. Both methods yield a single enhanced signal at each handpiece, where spurious peaks in the individual channels as well as stochastic noise are well suppressed in the output. Using the enhanced signals yields individual PTT estimates with a low spread compared to the baseline approach. While the enhancement is introduced in the context of PTT estimation, the approaches can be used to enhance signals in other biomedical applications of multi-channel LDV as well.

On-chip multi-beam frequency shifter through sideband separation.

In this paper, we introduce a novel method to realize a multi-beam optical frequency shifting component for photonic integrated circuits, utilizing an array of parallel optical modulators and a free-propagation region (FPR), such as a slab waveguide-based star coupler. This component generates multiple optical beams with different frequency shifts, making it suitable for various systems, such as multi-beam laser Doppler vibrometry (LDV). We thoroughly elaborate on the working principle of the component through theoretical analysis and demonstrate that by applying periodic wave-like modulation in the modulator array, the discrete harmonic content of the light can be selectively directed to different outputs based on the delay between consecutive modulators. A design comprising a 16-element modulator array and 5 outputs will be presented. Simulations show that this design can generate and collect 5 different harmonics (-2, -1, 0, +1, +2) in the different outputs with a side band suppression ratio of 20 dB to 30 dB for each output. Our proposed design is just one possibility and the component can be modified and optimized for specific applications.

UV photonic integrated circuits for far-field structured illumination autofluorescence microscopy.

Ultra-violet (UV) light has still a limited scope in optical microscopy despite its potential advantages over visible light in terms of optical resolution and of interaction with a wide variety of biological molecules. The main challenge is to control in a robust, compact and cost-effective way UV light beams at the level of a single optical spatial mode and concomitantly to minimize the light propagation loss. To tackle this challenge, we present here photonic integrated circuits made of aluminum oxide thin layers that are compatible with both UV light and high-volume manufacturing. These photonic circuits designed at a wavelength of 360 nm enable super-resolved structured illumination microscopy with conventional wide-field microscopes and without modifying the usual protocol for handling the object to be imaged. As a biological application, we show that our UV photonic chips enable to image the autofluorescence of yeast cells and reveal features unresolved with standard wide-field microscopy.

Miniaturization of Laser Doppler Vibrometers-A Review.

Laser Doppler vibrometry (LDV) is a non-contact vibration measurement technique based on the Doppler effect of the reflected laser beam. Thanks to its feature of high resolution and flexibility, LDV has been used in many different fields today. The miniaturization of the LDV systems is one important development direction for the current LDV systems that can enable many new applications. In this paper, we will review the state-of-the-art method on LDV miniaturization. Systems based on three miniaturization techniques will be discussed: photonic integrated circuit (PIC), self-mixing, and micro-electrochemical systems (MEMS). We will explain the basics of these techniques and summarize the reported miniaturized LDV systems. The advantages and disadvantages of these techniques will also be compared and discussed.

Pilot Testing of the "Turbidimeter", a Simple, Universal Reader Intended to Complement and Enhance Bacterial Growth Detection in Manual Blood Culture Systems in Low-Resource Settings.

Bloodstream infections and antimicrobial resistance are an increasing problem in low-income countries. There is a clear need for adapted diagnostic tools. To address this need, we developed a simple, universal reader prototype that detects bacterial growth in blood culture bottles. Our "turbidimeter" evaluates bacterial growth, based on the turbidity of the broth and the color change of the colorimetric CO2 indicator in commercially available blood culture bottles. A total of 60 measurements were performed using 10 relevant microbial species, spiked in horse blood, to compare the turbidimeter's performance with that of an automatic reference system. The turbidimeter was able to detect growth in all but one of the spiked blood culture bottles. In the majority (7/10) of the species tested, time-to-detection of the turbidimeter was shown to be non-inferior to the reference automated time-to-detection. This was, however, only the case when both the turbidity and color change in the colorimetric CO2-indicator were used to evaluate growth. We could not demonstrate the non-inferiority of the turbidity measurement alone. Overall, the turbidimeter performed well, but we also identified some improvements that will be implemented in the next version of the prototype.

A Miniaturised, Fully Integrated NDIR CO2 Sensor On-Chip.

In this paper, we present a fully integrated Non-dispersive Infrared (NDIR) CO2 sensor implemented on a silicon chip. The sensor is based on an integrating cylinder with access waveguides. A mid-IR LED is used as the optical source, and two mid-IR photodiodes are used as detectors. The fully integrated sensor is formed by wafer bonding of two silicon substrates. The fabricated sensor was evaluated by performing a CO2 concentration measurement, showing a limit of detection of ∼750 ppm. The cross-sensitivity of the sensor to water vapor was studied both experimentally and numerically. No notable water interference was observed in the experimental characterizations. Numerical simulations showed that the transmission change induced by water vapor absorption is much smaller than the detection limit of the sensor. A qualitative analysis on the long term stability of the sensor revealed that the long term stability of the sensor is subject to the temperature fluctuations in the laboratory. The use of relatively cheap LED and photodiodes bare chips, together with the wafer-level fabrication process of the sensor provides the potential for a low cost, highly miniaturized NDIR CO2 sensor.

Nonlinear signal errors in homodyne laser Doppler vibrometry induced by strong second-order ghost reflections and their mitigation.

A variety of mechanisms can induce distortions in the output signals of a homodyne laser Doppler vibrometer (LDV). In this paper, the nonlinear LDV distortions caused by a strong second-order ghost reflection originating from lens flares are theoretically explained and analyzed. We propose a simple compensation method to mitigate this distortion. The performance and limitations of this method are also explained both in simulation and in experiment.

Gold-induced photothermal background in on-chip surface enhanced stimulated Raman spectroscopy.

Surface enhanced Raman spectroscopy (SERS) and stimulated Raman spectroscopy (SRS) are well established techniques capable of boosting the strength of Raman scattering. The combination of both techniques (surface enhanced stimulated Raman spectroscopy, or SE-SRS) has been reported using plasmonic nanoparticles. In parallel, waveguide enhanced Raman spectroscopy has been developed using nanophotonic and nanoplasmonic waveguides. Here, we explore SE-SRS in nanoplasmonic waveguides. We demonstrate that a combined photothermal and thermo-optic effect in the gold material induces a strong background signal that limits the detection limit for the analyte. The experimental results are in line with theoretical estimates. We propose several methods to reduce or counteract this background.

Ultra-sensitive slot-waveguide-enhanced Raman spectroscopy for aqueous solutions of non-polar compounds using a functionalized silicon nitride photonic integrated circuit.

We demonstrate an ultra-sensitive waveguide-enhanced Raman sensor for low concentration organic compounds dissolved in water. The spectra are obtained using silicon nitride slot waveguides coated with a thin film of hexamethyldisilazane-modified mesoporous silica. Enriched locally by 600-fold within the coating, a micromolar level of cyclohexanone is probed. The sensor is also capable of simultaneous quantification of multiple analytes, and the adsorbed analytes can be completely released from the coating. These properties make this on-chip Raman sensor promising for diverse applications, especially for the monitoring of non-polar organics and biomolecules in aqueous environments.

Template Matching and Matrix Profile for Signal Quality Assessment of Carotid and Femoral Laser Doppler Vibrometer Signals.

Background: Laser-Doppler Vibrometry (LDV) is a laser-based technique that allows measuring the motion of moving targets with high spatial and temporal resolution. To demonstrate its use for the measurement of carotid-femoral pulse wave velocity, a prototype system was employed in a clinical feasibility study. Data were acquired for analysis without prior quality control. Real-time application, however, will require a real-time assessment of signal quality. In this study, we (1) use template matching and matrix profile for assessing the quality of these previously acquired signals; (2) analyze the nature and achievable quality of acquired signals at the carotid and femoral measuring site; (3) explore models for automated classification of signal quality. Methods: Laser-Doppler Vibrometry data were acquired in 100 subjects (50M/50F) and consisted of 4-5 sequences of 20-s recordings of skin displacement, differentiated two times to yield acceleration. Each recording consisted of data from 12 laser beams, yielding 410 carotid-femoral and 407 carotid-carotid recordings. Data quality was visually assessed on a 1-5 scale, and a subset of best quality data was used to construct an acceleration template for both measuring sites. The time-varying cross-correlation of the acceleration signals with the template was computed. A quality metric constructed on several features of this template matching was derived. Next, the matrix-profile technique was applied to identify recurring features in the measured time series and derived a similar quality metric. The statistical distribution of the metrics, and their correlates with basic clinical data were assessed. Finally, logistic-regression-based classifiers were developed and their ability to automatically classify LDV-signal quality was assessed. Results: Automated quality metrics correlated well with visual scores. Signal quality was negatively correlated with BMI for femoral recordings but not for carotid recordings. Logistic regression models based on both methods yielded an accuracy of minimally 80% for our carotid and femoral recording data, reaching 87% for the femoral data. Conclusion: Both template matching and matrix profile were found suitable methods for automated grading of LDV signal quality and were able to generate a quality metric that was on par with the signal quality assessment of the expert. The classifiers, developed with both quality metrics, showed their potential for future real-time implementation.

3D-printed optical probes for wafer-level testing of photonic integrated circuits.

Wafer-level probing of photonic integrated circuits is key to reliable process control and efficient performance assessment in advanced production workflows. In recent years, optical probing of surface-coupled devices such as vertical-cavity lasers, top-illuminated photodiodes, or silicon photonic circuits with surface-emitting grating couplers has seen great progress. In contrast to that, wafer-level probing of edge-emitting devices with hard-to-access vertical facets at the sidewalls of deep-etched dicing trenches still represents a major challenge. In this paper, we address this challenge by introducing a novel concept of optical probes based on 3D-printed freeform coupling elements that fit into deep-etched dicing trenches on the wafer surface. Exploiting the design freedom and the precision of two-photon laser lithography, the coupling elements can be adapted to a wide variety of mode-field sizes. We experimentally demonstrate the viability of the approach by coupling light to edge-emitting waveguides on different integration platforms such as silicon photonics (SiP), silicon nitride (TriPleX), and indium phosphide (InP). Achieving losses down to 1.9 dB per coupling interface, we believe that 3D-printed coupling elements represent a key step towards highly reproducible wafer-level testing of edge-coupled photonic integrated circuits.

Mitigation of photon background in nanoplasmonic all-on-chip Raman sensors.

In the quest for a more compact and cheaper Raman sensor, photonic integration and plasmonic enhancement are central. Nanoplasmonic slot waveguides exhibit the benefits of SERS substrates while being compatible with photonic integration and mass-scale (CMOS) fabrication. A difficulty in pursuing further integration of the Raman sensor with lasers, spectral filters, spectrometers and interconnecting waveguides lies in the presence of a photon background generated by the excitation laser field in any dielectric waveguide constituting those elements. Here, we show this problem can be mitigated by using a multi-mode interferometer and a nanoplasmonic slot waveguide operated in back-reflection to greatly suppress the excitation field behind the sensor while inducing very little photon background.

Silicon photonics-based laser Doppler vibrometer array for carotid-femoral pulse wave velocity (PWV) measurement.

Pulse wave velocity (PWV) is a reference measure for aortic stiffness, itself an important biomarker of cardiovascular risk. To enable low-cost and easy-to-use PWV measurement devices that can be used in routine clinical practice, we have designed several handheld PWV sensors using miniaturized laser Doppler vibrometer (LDV) arrays in a silicon photonics platform. The LDV-based PWV sensor design and the signal processing protocol to obtain pulse transit time (PTT) and carotid-femoral PWV in a feasibility study in humans, are described in this paper. Compared with a commercial reference PWV measurement system, measuring arterial pressure waveforms by applanation tonometry, LDV-based displacement signals resulted in more complex signals. However, we have shown that it is possible to identify reliable fiducial points for PTT calculation using the maximum of the 2nd derivative algorithm in LDV-based signals, comparable to those obtained by the reference technique, applanation tonometry.

Waveguide-based surface-enhanced Raman spectroscopy detection of protease activity using non-natural aromatic amino acids.

Surface enhanced Raman spectroscopy (SERS) is a selective and sensitive technique, which allows for the detection of protease activity by monitoring the cleavage of peptide substrates. Commonly used free-space based SERS substrates, however, require the use of bulky and expensive instrumentation, limiting their use to laboratory environments. An integrated photonics approach aims to implement various free-space optical components to a reliable, mass-reproducible and cheap photonic chip. We here demonstrate integrated SERS detection of trypsin activity using a nanoplasmonic slot waveguide as a waveguide-based SERS substrate. Despite the continuously improving SERS performance of the waveguide-based SERS substrates, they currently still do not reach the SERS enhancements of free-space substrates. To mitigate this, we developed an improved peptide substrate in which we incorporated the non-natural aromatic amino acid 4-cyano-phenylalanine, which provides a high intrinsic SERS signal. The use of non-natural aromatics is expected to extend the possibilities for multiplexing measurements, where the activity of several proteases can be detected simultaneously.

Transfer-print integration of GaAs p-i-n photodiodes onto silicon nitride waveguides for near-infrared applications.

We demonstrate waveguide-detector coupling through the integration of GaAs p-i-n photodiodes (PDs) on top of silicon nitride grating couplers (GCs) by means of transfer-printing. Both single device and arrayed printing is demonstrated. The photodiodes exhibit dark currents below 20 pA and waveguide-referred responsivities of up to 0.30 A/W at 2V reverse bias, corresponding to an external quantum efficiency of 47% at 860 nm. We have integrated the detectors on top of a 10-channel on-chip arrayed waveguide grating (AWG) spectrometer, made in the commercially available imec BioPIX-300 nm platform.

On-Chip Non-Dispersive Infrared CO2 Sensor Based On an Integrating Cylinder.

In this paper, we propose a novel, miniaturized non-dispersive infrared (NDIR) CO2 sensor implemented on a silicon chip. The sensor has a simple structure, consisting of a hollow metallic cylindrical cavity along with access waveguides. A detailed analysis of the proposed sensor is presented. Simulation with 3D ray tracing shows that an integrating cylinder with 4 mm diameter gives an equivalent optical path length of 3 . 5 cm. The sensor is fabricated using Deep Reactive Ion Etching (DRIE) and wafer bonding. The fabricated sensor was evaluated by performing a CO2 concentration measurement, showing a limit of detection of ∼100 ppm. The response time of the sensor is only ∼2.8 s, due to its small footprint. The use of DRIE-based waveguide structures enables mass fabrication, as well as the potential co-integration of flip-chip integrated midIR light-emitting diodes (LEDs) and photodetectors, resulting in a compact, low-power, and low-cost NDIR CO2 sensor.

Comparison of Free-Space and Waveguide-Based SERS Platforms.

Surface-Enhanced Raman Spectroscopy (SERS) allows for the highly specific detection of molecules by enhancing the inherently weak Raman signals near the surface of plasmonic nanostructures. A variety of plasmonic nanostructures have been developed for SERS signal excitation and collection in a conventional free-space microscope, among which the gold nanodomes offer one of the highest SERS enhancements. Nanophotonic waveguides have recently emerged as an alternative to the conventional Raman microscope as they can be used to efficiently excite and collect Raman signals. Integration of plasmonic structures on nanophotonic waveguides enables reproducible waveguide-based excitation and collection of SERS spectra, such as in nanoplasmonic slot waveguides. In this paper, we compare the SERS performance of gold nanodomes, in which the signal is excited and collected in free space, and waveguide-based nanoplasmonic slot waveguide. We evaluate the SERS signal enhancement and the SERS background of the different SERS platforms using a monolayer of nitrothiophenol. We show that the nanoplasmonic slot waveguide approaches the gold nanodomes in terms of the signal-to-background ratio. We additionally demonstrate the first-time detection of a peptide monolayer on a waveguide-based SERS platform, paving the way towards the SERS monitoring of biologically relevant molecules on an integrated lab-on-a-chip platform.

Plasma-Enhanced Atomic Layer Deposition of Nanostructured Gold Near Room Temperature.

A plasma-enhanced atomic layer deposition (PE-ALD) process to deposit metallic gold is reported, using the previously reported Me3Au(PMe3) precursor with H2 plasma as the reactant. The process has a deposition window from 50 to 120 °C with a growth rate of 0.030 ± 0.002 nm per cycle on gold seed layers, and it shows saturating behavior for both the precursor and reactant exposure. X-ray photoelectron spectroscopy measurements show that the gold films deposited at 120 °C are of higher purity than the previously reported ones (<1 at. % carbon and oxygen impurities and <0.1 at. % phosphorous). A low resistivity value was obtained (5.9 ± 0.3 µΩ cm), and X-ray diffraction measurements confirm that films deposited at 50 and 120 °C are polycrystalline. The process forms gold nanoparticles on oxide surfaces, which coalesce into wormlike nanostructures during deposition. Nanostructures grown at 120 °C are evaluated as substrates for free-space surface-enhanced Raman spectroscopy (SERS) and exhibit an excellent enhancement factor that is without optimization, only one order of magnitude weaker than state-of-the-art gold nanodome substrates. The reported gold PE-ALD process therefore offers a deposition method to create SERS substrates that are template-free and does not require lithography. Using this process, it is possible to deposit nanostructured gold layers at low temperatures on complex three-dimensional (3D) substrates, opening up opportunities for the application of gold ALD in flexible electronics, heterogeneous catalysis, or the preparation of 3D SERS substrates.

High index contrast photonic platforms for on-chip Raman spectroscopy.

Nanophotonic waveguide enhanced Raman spectroscopy (NWERS) is a sensing technique that uses a highly confined waveguide mode to excite and collect the Raman scattered signal from molecules in close vicinity of the waveguide. The most important parameters defining the figure of merit of an NWERS sensor include its ability to collect the Raman signal from an analyte, i.e. "the Raman conversion efficiency" and the amount of "Raman background" generated from the guiding material. Here, we compare different photonic integrated circuit (PIC) platforms capable of on-chip Raman sensing in terms of the aforementioned parameters. Among the four photonic platforms under study, tantalum oxide and silicon nitride waveguides exhibit high signal collection efficiency and low Raman background. In contrast, the performance of titania and alumina waveguides suffers from a strong Raman background and a weak signal collection efficiency, respectively.

High-power single transverse and polarization mode VCSEL for silicon photonics integration.

We demonstrate a 6.5 mW single transverse and polarization mode GaAs-based oxide-confined VCSEL at 850 nm. High power is enabled by a relatively large oxide aperture and an epitaxial design for low resistance, low optical loss, and high slope efficiency VCSELs. With the oxide aperture supporting multiple polarization unrestrained transverse modes, single transverse and polarization mode operation is achieved by a transverse and polarization mode filter etched into the surface of the VCSEL. While the VCSEL is specifically designed for light source integration on a silicon photonic integrated circuit, its performance in terms of power, spectral purity, polarization, and beam properties are of great interest for a large range of applications.