In the domain of ultrasonically powered biomedical implants, there is an increasing interest in cm-scale ultrasonic receivers (RX). However, when a single-element transducer is used as the RX transducer, an uneven phase distribution across the RX area can significantly reduce the harvestable power. In this paper, we investigate the impact of lateral and angular misalignment on the acoustic field phase distribution across the RX surface. We show that, for a single-element RX transducer, lateral misalignment has minimal effect on the harvestable power, whereas even small angular misalignments can cause a considerable reduction, especially for larger RX sizes. We present a potential solution that consists of subdividing a large RX transducer (e.g. 20 × 20mm2) into smaller elements, which significantly improves power transfer efficiency by taking advantage of the smaller phase variation across the surface of each element. The trade-offs between achieving a minimum acceptable power transfer efficiency and managing the increased complexity in packaging and matching circuitry are also discussed. @en

Aluminum Nitride (AlN) Piezoelectric Micromachined Ultrasonic Transducers (PMUTs) are gaining interest for biomedical implant power due to biocompatibility and lowtemperature processing. However, due to the low piezoelectric coefficient of AlN PMUTs, storage capacitors are often used to accumulate ultrasonic power transferred over an extended time. The accumulated energy is then used to power a DC load, which leads to a long start-up time, and insufficient duty cycle for some applications. We present an ultrasonically powered system for biomedical implants capable of delivering mW-range instantaneous power to DC loads, without pre-storing it. The system features a 25 mm2 AlN PMUT, an inductive matching network, and an application-specific power management integrated circuit(ASIC). For an acoustic intensity of 360 mW/cm2 at the surface of the PMUT, an open-circuit voltage of 1.11 V and an aperture efficiency of 30.5 % are measured. Furthermore, by connecting a series-matching inductor to the PMUT, the highest-reported power delivered to the load (PDL) of 6.4 mW is measured over an optimal load of 7.6 Ω. Finally, together with the ASIC and at the intensity of 108 mW/cm2, our system delivers 1.04 mW DC power to a 3.3 kΩ load, which is over two orders of magnitude higher than the previously reported average DC power for AlN PMUTs. @en

Capacitive micromachined ultrasonic transducers (CMUTs) with a built-in charge layer are known as a pre-charged CMUT. In our prior work, we have shown how to model and characterize the charges inside the pre-charged collapse-mode CMUT and conducted life-time test that showed that the charges trapped inside the dielectric were stable in the order of years [1]. However, our prior work focused on the use of pre-charged collapse-mode CMUTs as a way to achieve ultrasound power reception, which does not require the CMUT to be actively driven. In this work, for the first time we use pre-charged collapse-mode CMUTs with an Al2O3 charge-trapping layer to create a B-mode ultrasound image. Thus, this work shows the first example that pre-charged collapse-mode CMUTs can fully operate with only an AC voltage.@en

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.@en

Capacitive Micromachined Ultrasound Transducers (CMUTs) have many advantages compared to other ultrasonic transducer technologies, especially for implantable devices. However, they require a high bias voltage for efficient operation. To eliminate the need for an external bias voltage, a charge storage layer can be embedded in the dielectric. This study aims to compare the performance of Si 3 N 4 and Al 2 O 3 when used as a charge storage layer. By measuring the shift in the C-V curve, Si 3 N 4 exhibits a larger shift than Al 2 O 3 , indicating a better charge-trapping capability. When using the pre-charged CMUTs as power receivers, the Si 3 N 4 version harvested up to 80 mW -only a few mW more than the Al 2 O 3 - with an efficiency of about 50 %. Accelerated Lifetime Tests predict a lifetime of about 7.8 and 1.2 years for Si 3 N 4 and Al 2 O 3 respectively.@en

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 size 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 μm × 280 μm × 420 μm 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 μm 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.

@en

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.@en

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.

@en

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.

@en

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.@en

Recently, focused ultrasound has been proposed to power deeply implanted medical devices. Almost exclusively, lead zirconate titanate (PZT) transducers are used to convert acoustic energy into electrical energy. Unfortunately, these lead containing devices cannot be hermetically encapsulated since that would block the ultrasound. We propose the use of biocompatible Capacitive Micromachined Ultrasonic Transducer (CMUT) elements to replace traditional PZT transducers. In addition, to eliminate the external bias voltage, we introduced a charge trapping Al2O3 layer inside the CMUT to create a built-in bias voltage. These devices can be pre-charged and used as a receiver for US power. In this work, the viability of charged CMUTs to power deep implants was explored by investigating the effect of the charging parameters and by performing Accelerated Lifetime Tests (ALT). The estimated lifetime at body temperature ranges between 2.5 to 3.5 years at body temperature, which significantly depends on the charging parameters.@en

One of the many applications of organ-on-a-chip (OOC) technology is the study of biological processes in human induced pluripotent stem cells (iPSCs) during pharmacological drug screening. It is of paramount importance to construct OOCs equipped with highly compact in situ sensors that can accurately monitor, in real time, the extracellular fluid environment and anticipate any vital physiological changes of the culture. In this paper, we report the co-fabrication of a CMOS smart sensor on the same substrate as our silicon-based OOC for real-time in situ temperature measurement of the cell culture. The proposed CMOS circuit is developed to provide the first monolithically integrated in situ smart temperature-sensing system on a micromachined silicon-based OOC device. Measurement results on wafer reveal a resolution of less than ±0.2 °C and a nonlinearity error of less than 0.05% across a temperature range from 30 to 40 °C. The sensor's time response is more than 10 times faster than the time constant of the convection-cooling mechanism found for a medium containing 0.4 ml of PBS solution. All in all, this work is the first step towards realizing OOCs with seamless integrated CMOS-based sensors capable to measure, in real time, multiple physical quantities found in cell culture experiments. It is expected that the use of commercial foundry CMOS processes may enable OOCs with very large scale of multi-sensing integration and actuation in a closed-loop system manner.

@en

Several Silicon on Insulator (SOI) wafer manufacturers are now offering products with customer‐defined cavities etched in the handle wafer, which significantly simplifies the fabrication of MEMS devices such as pressure sensors. This paper presents a novel cavity buried oxide (BOX) SOI substrate (cavity‐BOX) that contains a patterned BOX layer. The patterned BOX can form a buried microchannels network, or serve as a stop layer and a buried hard‐etch mask, to accurately pattern the device layer while etching it from the backside of the wafer using the cleanroom microfab-rication compatible tools and methods. The use of the cavity‐BOX as a buried hard‐etch mask is demonstrated by applying it for the fabrication of a deep brain stimulation (DBS) demonstrator. The demonstrator consists of a large flexible area and precisely defined 80 μm‐thick silicon islands wrapped into a 1.4 mm diameter cylinder. With cavity‐BOX, the process of thinning and separating the silicon islands was largely simplified and became more robust. This test case illustrates how cavity‐BOX wafers can advance the fabrication of various MEMS devices, especially those with complex geometry and added functionality, by enabling more design freedom and easing the optimization of the fabrication process.

@en

Stemming from the convergence of tissue engineering and microfluidics, organ-on-chip (OoC) technology can reproduce in vivo-like dynamic microphysiological environments for tissues in vitro. The possibility afforded by OoC devices of realistic recapitulation of tissue and organ (patho)physiology may hold the key to bridge the current translational gap in drug development, and possibly foster personalized medicine. Here we underline the biotechnological convergence at the root of OoC technology, and outline research tracks under development in our group at TU Delft along two main directions: fabrication of innovative microelectromechanical OoC devices, integrating stimulation and sensing of tissue activity, and their embedding within advanced platforms for pre-clinical research. We conclude with remarks on the role of open technology platforms for the broader establishment of OoC technology in pre-clinical research and drug development.@en

Using ultrasound to power deeply implanted biomedical devices is a promising technique due to its low attenuation in body tissue and its short wavelength that allows precise focusing of the energy. Ultrasound energy harvesting conventionally has been done using lead zirconate titanate (PZT) ultrasound transducers, which uses the piezoelectric effect to convert mechanical vibration to an electrical voltage. However, PZT is typically bulky, and is not bio-compatible, and cannot be monolithically integrated with application-specific integrated circuits (ASIC). In this work, a pre-charged collapse-mode capacitive micromachined ultrasonic transducer (CMUT) was fabricated to harvest ultrasound energy. The pre-charged CMUT has a high power transfer efficiency over a wide bandwidth at optimal loading conditions; 43% at 2.15 MHz and 47% at 5.85 MHz. For the last 1.4 years, the device has been in collapse-mode, and it is still functional without any additional charging. This device will enable the development of smaller implantable biomedical devices in the future.@en

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 (SiO2 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 SiO2 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.@en

Implantable medical devices are becoming smaller and more deeply implanted in the human body for various applications (i.e., neurostimulation, drug delivery, bone fracture monitoring). Therefore, an efficient ultrasound power transfer link is needed to charge these devices. However, this is challenging because each ultrasound transducer has limited angular sensitivity. This work proposes a low-power telemetry protocol that can reliably feedback the power sent to the implant with backscattered ultrasound. The protocol works by sending two consecutive interrogation signals and connecting a circuit on the receiver that modulates only one of the two signals. The modulated signal can be decoded with an external ultrasound probe. In this work, the circuit was built, verified, and compared with simulation results. It was shown that the telemetry protocol could accurately localize the receiving ultrasound element at sub-mm precision at a 10 cm depth.@en

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.@en

Recent advances in MEMS technology have brought forward a new class of high-density stretchable/flexible electronics as well as large displacement MEMS devices. The in-situ electro-mechanical characterization of such devices is challenging since it requires: (i) highly delicate sample handling, (ii) controlled application of large (hundreds of µm) multi-axial displacements to mimic service conditions, (iii) integrated electrical testing and (iv) fast actuation for cyclic testing. Techniques already developed for small-scale testing in literature fall short to meet the combined set of requirements. To this end, a characterization methodology that fulfills all these requirements is developed and presented here. The technique is based on a piezo-driven micro-tensile stage, which provides large multi-axial displacements with high resolution and fast actuation (4000 µm/s). This is combined with a method for sample microfabrication on a test-chip to warrant delicate sample handling. Proof-of-principle experiments are shown for multi-axial mechanical characterization, electrical characterization and high cycle fatigue testing of micron-sized highly stretchable interconnects. Experiments are conducted under in-situ microscopic observation using optical microscopy, scanning electron microscopy, and high-resolution profilometry. The generic platform proposed here can be used for other problems where similar requirements are faced, e.g. other miniaturized, large displacement electro-mechanical applications that are currently being developed.@en

Parylene-C has been used as a substrate and encapsulation material for many implantable medical devices. However, to ensure the flexibility required in some applications, minimize tissue reaction, and protect parylene from degradation in vivo an additional outmost layer of polydimethylsiloxane (PDMS) is desired. In such a scenario, the adhesion of PDMS to parylene is of critical importance to prevent early failure caused by delamination in the harsh environment of the human body. Towards this goal, we propose a method based on creating chemical covalent bonds using intermediate ceramic layers as adhesion promoters between PDMS and parylene.To evaluate our concept, we prepared three different sets of samples with PDMS on parylene without and with oxygen plasma treatment (the most commonly employed method to increase adhesion), and samples with our proposed ceramic intermediate layers of silicon carbide (SiC) and silicon dioxide (SiO₂). The samples were soaked in phosphate-buffered saline (PBS) solution at room temperature and were inspected under an optical microscope. To investigate the adhesion property, cross-cut tape tests and peel tests were performed. The results showed a significant improvement of the adhesion and in-soak long-term performance of our proposed encapsulation stack compared with PDMS on parylene and PDMS on plasma-treated parylene. We aim to use the proposed solution to package bare silicon chips on active implants.

@en