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In this paper, we present a flip-chip bonding concept for InP die on SiN-based TriPleX carrier using laser soldering. The InP die and SiN-based TriPleX carrier include the metalization patterns for commonly used photonic integrated circuit reference designs. Two laser soldering schemes were investigated: (1) using a laser wavelength where silicon is highly transmissive (through-silicon laser soldering) and (2) using a laser wavelength where silicon is not transmissive (heat-conduction laser soldering). We demonstrated a 4.0 mm × 4.6 mm InP die with 58 electrical connections flip-chip bonded on a 16.0 mm × 8.0 mm SiN-based TriPleX carrier. Comparison experiments were carried out including solder reflow and shear force tests. Both schemes showed reliable electrical interconnects that meet MIL-STD 883 standards. Especially, the through-silicon soldering showed faster soldering time, lower power for solder reflows, and less thermal impact which is therefore preferred over heat-conduction soldering. This concept is promising for a high-density, reliable interconnect of hybrid packaging of InP on SiN-based photonic integrated circuits, in particular large photonic dies.

Optimal treatment of cancer requires diagnostic methods to facilitate therapy choice and prevent ineffective treatments. Direct assessment of therapy response in viable tumor specimens could fill this diagnostic gap. Therefore, we designed a microfluidic platform for assessment of patient treatment response using tumor tissue slices under precisely controlled growth conditions. The optimized Cancer-on-Chip (CoC) platform maintained viability and sustained proliferation of breast and prostate tumor slices for 7 days. No major changes in tissue morphology or gene expression patterns were observed within this time frame, suggesting that the CoC system provides a reliable and effective way to probe intrinsic chemotherapeutic sensitivity of tumors. The customized CoC platform accurately predicted cisplatin and apalutamide treatment response in breast and prostate tumor xenograft models, respectively. The culture period for breast cancer could be extended up to 14 days without major changes in tissue morphology and viability. These culture characteristics enable assessment of treatment outcomes and open possibilities for detailed mechanistic studies.Significance:The Cancer-on-Chip platform with a 6-well plate design incorporating silicon-based microfluidics can enable optimal patient-specific treatment strategies through parallel culture of multiple tumor slices and diagnostic assays using primary tumor material.

Supplementary files

Hybrid integrated diode lasers offer a robust and small-sized solution for applications in telecommunications, quantum optics and metrology due to their wide tunability and ultra-narrow linewidth. Here, we present the fabrication, packaging and successful operation of the first fully integrated, aluminum oxide (Al2O3) based, hybrid diode laser operating at 405 nm. Low-loss, high-confinement waveguides are fabricated with a measured propagation loss of only 2.8 ± 0.3 dB/cm. The hybrid laser consists of a GaN SLED butt-coupled to an Al2O3 feedback circuit comprising of two microring resonators that form a frequency selective Vernier filter. The chip assembly is packaged in a hermetically sealed, butterfly housing for optimal performance and durability. The laser shows a maximum output power of 0.74 mW and is tunable over the entire gain bandwidth of 4.4 nm.

The digitization of smart catheters will dramatically increase the demand for reliable and high data transmission in the distal tips. Optical fiber is a good candidate to provide high-speed data transmission. However, the extremely small scale of the smart catheter tip, with less than a few millimeters in diameter, hampers the integration of optical fiber connections in the catheter tip. Our work presents a stand-alone optical data link module (ODLM) with a dimension of 240 m 280 m 420 m for use in a 1 mm diameter intravascular ultrasound (IVUS) smart catheter. The fabrication of the ODLM is based on the Flex-to-Rigid (F2R) integration technology. In the ODLM, the flexible interconnects reroute the electrical contacts of the flip-chipped vertical-cavity sur-face-emitting laser (VCSEL) to the side of the device. This design enables the ODLM to be mounted on a flex-PCB and fit into a 200-300 m gap in the IVUS catheter tip. An optical fiber that runs parallel to the catheter shaft is self-aligned to a commercially available VCSEL by inserting it into the through-silicon hole (TSH) of the ODLM. Clear eye diagrams prove the stand-alone ODLM can transmit 25.8 Gb/s, 231-1 Pseudo-Random Binary Sequence (PRBS) when driven through a high-speed bias-tee. The BER test indicates that error-free operation can be achieved at an optical output of around -4 dBm.

Background Microelectrode arrays (MEA) enable the measurement and stimulation of the electrical activity of cultured cells. The integration of other neuromodulation methods will significantly enhance the application range of MEAs to study their effects on neurons. A neuromodulation method that is recently gaining more attention is focused ultrasound neuromodulation (FUS), which has the potential to treat neurological disorders reversibly and precisely. Methods In this work, we present the integration of a focused ultrasound delivery system with a multiwell MEA plate. Results The ultrasound delivery system was characterised by ultrasound pressure measurements, and the integration with the MEA plate was modelled with finite-element simulations of acoustic field parameters. The results of the simulations were validated with experimental visualisation of the ultrasound field with Schlieren imaging. In addition, the system was tested on a murine primary hippocampal neuron culture, showing that ultrasound can influence the activity of the neurons. Conclusions Our system was demonstrated to be suitable for studying the effect of focused ultrasound on neuronal cultures. The system allows reproducible experiments across the wells due to its robustness and simplicity of operation.

Recently, the applications of ultrasound transducers expanded from high-end diagnostic tools to point of care diagnostic devices and wireless power receivers for implantable devices. These new applications additionally require that the transducer technology must comply to biocompatibility and manufacturing scalability. In this respect, Capacitive Micromachined Ultrasound Transducers (CMUTs) have a strong advantage compared to the conventional PZT based transducers. However, current CMUTs require a large DC bias voltage for their operation, which limits the miniaturizability of these devices. In this study, we propose a pre-charged collapse-mode CMUT for immersive applications that can operate without an external bias by means of a charge trapping Al2O3 layer embedded in the dielectrics between the top and bottom electrodes. The built-in charge layer was analytically modeled and four layer stack combinations were investigated and characterized. The measurement results of the CMUTs were then used to fit the model and to quantify the amount and type of trapped charge. It was found that these devices polarize due to the ferroelectric-like behavior of the Al2O3, and the amount of charge stored in the charge-trapping layer was estimated to be approximately 0.02 C/m2. Their acoustic performance shows a transmit and receive sensitivity of 8.8 kPa/V and 13.1 V/MPa respectively. In addition, we show that increasing the charging temperature, the charging duration, and the charging voltage results in a higher amount of stored charge. Finally, results of ALT tests showed that these devices have a lifetime of more than 2.5 years at body temperature.

Combining optical gain in direct-bandgap III-V materials with tunable optical feedback offered by advanced photonic integrated circuits is key to chip-scale external-cavity lasers (ECL), offering wideband tunability along with low optical linewidths. External feedback circuits can be efficiently implemented using low-loss silicon nitride (Si$_3$ N$_4$) waveguides, which do not suffer from two-photon absorption and can thus handle much higher power levels than conventional silicon photonics. However, co-integrating III-V-based gain elements with tunable external feedback circuits in chip-scale modules still represents a challenge, requiring either technologically demanding heterogeneous integration techniques or costly high-precision multi-chip assembly, often based on active alignment. In this work, we demonstrate Si$_3$N$_4$-based hybrid integrated ECL that exploit 3D-printed structures such as intra-cavity photonic wire bonds and facet-attached microlenses for low-loss optical coupling with relaxed alignment tolerances, thereby overcoming the need for active alignment while maintaining the full flexibility of multi-chip integration techniques. In a proof-of-concept experiment, we demonstrate an ECL offering a 90 nm tuning range (1480 nm–1570 nm) with on-chip output powers above 12 dBm and side-mode suppression ratios of up to 59 dB in the center of the tuning range. We achieve an intrinsic linewidth of 979 Hz, which is among the lowest values reported for comparable feedback architectures. The optical loss of the intra-cavity photonic wire bond between the III-V gain element and the Si$_3$N$_4$-based tunable feedback circuit amounts to approximately (1.6 ± 0.2) dB. We use the ECL as a tunable pump laser to generate a dissipative Kerr soliton frequency comb. To the best of our knowledge, our experiments represent the first demonstration of a single-soliton Kerr comb generated with a pump that is derived from a hybrid ECL.

Optimal treatment of cancer requires diagnostic methods to facilitate therapy choice and prevent ineffective treatments. Direct assessment of therapy response in viable tumor specimens could fill this diagnostic gap. Therefore, we designed a microfluidic platform for assessment of patient treatment response using tumor tissue slices under precisely controlled growth conditions. The optimized Cancer-on-Chip (CoC) platform maintained viability and sustained proliferation of breast and prostate tumor slices for 7 days. No major changes in tissue morphology or gene expression patterns were observed within this time frame, suggesting that the CoC system provides a reliable and effective way to probe intrinsic chemotherapeutic sensitivity of tumors. The customized CoC platform accurately predicted cisplatin and apalutamide treatment response in breast and prostate tumor xenograft models, respectively. The culture period for breast cancer could be extended up to 14 days without major changes in tissue morphology and viability. These culture characteristics enable assessment of treatment outcomes and open possibilities for detailed mechanistic studies. Significance: The Cancer-on-Chip platform with a 6-well plate design incorporating silicon-based microfluidics can enable optimal patient-specific treatment strategies through parallel culture of multiple tumor slices and diagnostic assays using primary tumor material.

Terabit capacity optical engines for data center and access networks are gaining momentum supported by a pool of technological innovations that are promising low cost and simple design for a wide range of application use cases.

We demonstrate a flow cytometer in which structured light illumination is used to attribute fluorescent and scattering signals to their excitation wavelength. A suitable multi-color light source emitting structured illumination patterns at 405, 488, 561 and 640 nm is developed based on a silicon nitride photonic integrated circuit and cytometry experiments are conducted with calibration beads. Performance metrics of the novel cytometer are compared with those of a mature, commercial device. While the experimental device still features a slightly higher sensitivity floor than the commercial one, all but the most weakly stained beads can be categorized. These promising results validate the feasibility of the proposed concept.

We demonstrate a stand-alone optical data link module (ODLM) that fits in the limited space budget of smart imaging catheters. The module is based on an extension of the Flex-to-Rigid (F2R) technology platform for miniaturized system integration. The ODLM is a silicon-based interposer that comprises a commercially available Vertical Cavity Surface Emitting Laser (VCSEL), which has its electrical contacts and laser emitting spot on the same surface. With the flexible interconnects, the ODLM reroutes the flip-chipped VCSEL electrical contacts to the side that is perpendicular to the surface of the VCSEL. This enables the ODLM to be mounted on a flex-PCB and fit into the limited space in the distal tip of the smart catheter. An optical fiber that runs in parallel to the catheter shaft is inserted into the through-silicon hole (TSH) of the ODLM and self-aligned to the VCSEL for optical data transmission. The design of the ODLM and the F2R technology platform are introduced, and an ODLM demonstrator is fabricated and presented.

We present our hybrid InP to SiN TriPleX integration interface with a novel alignment technique and its application to complex photonic integrated circuits. The integration interface comprises vertical alignment stops, which simplify the alignment process and allow for array integration with the same simplicity as for single dies. Horizontal alignment is carried out by utilizing optical backscatter reflectometry to get an active feedback signal without the need to operate the chip. Thus, typical contacting limitations of active flip-chip alignment are overcome. By using this method, we demonstrate the integration of InP DFB lasers with more than 60 mW of optical power coupled to a SiN waveguide with an averaged coupling loss of -2.1 dB. The hybrid integration process is demonstrated for single dies as well as full arrays. We evaluate the feasibility of the assembly process for complex photonic integrated circuits by integrating an InP gain chip to a SiN TriPleX external cavity. The process proves to be well suited and allows monitoring chip quality during assembly. A fully functional hybrid integrated tunable laser is fabricated, which is capable of full C-band tuning with optical output power of up to 60 mW.

We present the first Organ-on-Chip equipped with a low-impedance Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) MicroElectrode Array (MEA). The novel device allows simultaneous mechanical stimulation with a stretchable PDMS membrane and electrical monitoring via the PEDOT:PSS MEA of multiple in vitro cell cultures. The surface area enhancement and the morphology of the PEDOT:PSS allows an increase of the charge injection per unit area at the electrode-electrolyte interface, resulting in significantly lower electrochemical impedance of the electrodes. In particular, at 1 kHz the fabricated PEDOT-MEA electrodes show a reduction of the overall impedance up to 99.4 and 93.3 % in comparison with benchmark TiN and Pt electrodes. The superior performance of PEDOT:PSS were also confirmed via Cyclic Voltammetry measurement, in which PEDOT:PSS showed a very large capacitive current, compared with the benchmark electrodes both in the forward and the reverse scans. The obtained results confirm the effectiveness of the proposed PEDOT:PSS coating, and introduce this material in the OOC field. Moreover, the quality and morphology of the fabricated PEDOT:PSS based electrodes were assessed via SEM imaging and Raman spectroscopy.

The main limitation of acoustic particle separation for microfluidic application is its low sorting efficiency. This is due to the weak coupling of surface acoustic waves (SAWs) into the microchannel. In this work, we demonstrate bulk acoustic wave (BAW) particle sorting using capacitive micromachined ultrasonic transducers (CMUTs) for the first time. A collapsed mode CMUT was driven in air to generate acoustic pressure within the silicon substrate in the in-plane direction of the silicon die. This acoustic pressure was coupled into a water droplet, positioned at the side of the CMUT die, and measured with an optical hydrophone. By using a beam steering approach, the ultrasound generated from 32 CMUT elements were added in-phase to generate a maximum peak-to-peak pressure of 0.9 MPa. Using this pressure, 10 µm latex beads were sorted almost instantaneously.

Ultrasound (US) has recently gained attention for powering and communication with implantable devices due to its short wavelength and low attenuation. However, beam mis-alignments cause a sharp decrease in the amount of transferred power and quality of communication. This work investigates a telemetry protocol that relies on the difference in the phase of the received backscattered signal to precisely focus the US on the implantable device and track it over time. The interrogation signal is generated by a linear phased array probe, and the receiver is a pre-charged collapse-mode Capacitive Micromachined Ultrasound Transducer (CMUT) connected to a load modulation circuit. Using the time/phase reversal tracking algorithm, the RX was located within 300 ms after the first modulation was detected. The ability of the algorithm to track the RX while it is moving was also tested, showing that it can reliably track it up to a speed of 1 mm/s.

Generating visible light with wide tunability and high coherence based on photonic integrated circuits is of high interest for applications in biophotonics, precision metrology and quantum technology. Here we present the first demonstration of a hybrid-integrated diode laser in the visible spectral range. Using an AlGaInP optical amplifier coupled to a low-loss Si3N4 feedback circuit based on microring resonators, we obtain a spectral coverage of 10.8 nm around 684.4 nm wavelength with up to 4.8 mW output power. The measured intrinsic linewidth is 2.3$\pm$0.2 kHz., Comment: 8 pages, 6 figures

In this paper, we investigate the long-term adhesion strength and barrier property of our recently proposed encapsulation stack that includes PDMS-Parylene C and PECVD interlayers (SiO 2 and SiC) for adhesion improvement. To evaluate the adhesion strength of our proposed stack, the sample preparation consisted in depositing approximately 25 nm of SiC and 25 nm of SiO 2 on half wafers, previously coated with Parylene C. Next, $50 \mu \mathrm{m}$ PDMS was spin-coated on top. Finally, the samples were detached from the Si wafer and soaked in a PBS solution at 67°C to accelerate the aging process. Two samples were also implanted, subcutaneously, on the left and right subscapular regions of a rat. The optical inspection and peel tests performed after two months confirmed our preliminary findings and showed a significant improvement of the adhesion in our proposed encapsulation stack compared to the case of PDMS on Parylene C alone. In addition, the X-ray photoelectron spectroscopy(XPS) analysis at the interface between SiC and Parylene C showed different peaks for the interface compared to the reference spectra, which could be an indication of a chemical bond. Finally, water vapor transmission rate (WVTR) tests were performed to investigate the barrier property of our proposed encapsulation stack against water vapor transmission. The results demonstrated that the proposed stack acts as a significantly (two orders of magnitude) higher barrier against moisture compared to only Parylene C and PDMS encapsulation layers. The proposed method yields a fully transparent encapsulation stack over a broad wavelength spectrum that can be used for the conformal encapsulation of flexible devices and thus, making them compatible with techniques such as optical imaging and optogenetics.