This study comprehensively examines the barrier properties, aging behavior, and failure mechanisms of Parylene F-VT4 films, applied at four distinct thicknesses (0.3 µm, 0.6 µm, 0.9 µm, and 1.2 µm), as encapsulation layers for implantable medical devices. Parylene F-VT4, a fluorinated polymer known for its mechanical flexibility, thermal stability, and chemical inertness, is a promising candidate for long-term hermetic encapsulation. Parylene F-VT4 was uniformly deposited via a dedicated chemical vapor deposition (CVD) process typically used for Parylene depositions. The investigation of the Parylene F-VT4 films included pinhole density characterization, electrochemical impedance spectroscopy (EIS), and testing of coating lifetime based on the resistance of Cu meanders protected by Parylene F-VT4 when immersed in phosphate-buffered saline (PBS) under accelerated aging conditions (PBS at 60 °C) over 550 days. The EIS results demonstrated that thicker coatings (1.2 µm) exhibited excellent barrier properties and resistance to electrolyte penetration, whereas thinner coatings (0.3 µm and 0.6 µm) showed more rapid degradation due to microvoids and pinholes. The temporal evaluation of EIS spectra highlighted the gradual decrease in impedance magnitude, indicating the ingress of ions and water into the coating. The lifetime in PBS at 60 °C was determined by resistance-based lifetime measurements on Cu meander structures coated with Parylene F-VT4 coatings. The lifetime at 37 °C was calculated, assuming an acceleration factor of 2 per 10 °C increase in temperature, yielding lifetimes of approximately 25 days, 6.4 months, 2.3 years, and 4.5 years for 0.3 µm, 0.6 µm, 0.9 µm, and 1.2 µm coatings, respectively. These findings highlight the critical relationship between thickness and durability, providing valuable insights into the long-term performance of thin Parylene F-VT4 films for implantable devices.

The motivation of this work is to enable the use of piezoelectric micromachined ultrasonic transducer (PMUT)-based implants within the human body for biomedical applications, particularly for power and data transfer for implanted medical devices. To protect surrounding tissue and ensure PMUT functionality over time, biocompatible and hermetic encapsulation is essential. This study investigates the impact of Parylene F-VT4 layers of various thicknesses as well as the effect of multilayer stacks of Parylene F-VT4 combined with atomic layer-deposited nanolayers of Al2O3 and HfO2 on the mechanical and acoustic properties of PMUTs. PMUTs with various diameters (40 µm, 60 µm, and 80 µm) are fabricated and tested both as stand-alone devices and as arrays. The mechanical behavior of single stand-alone PMUT devices is characterized in air and in water using laser Doppler vibrometry (LDV), while the acoustic output of arrays is evaluated by pressure measurements in water. Experimental results reveal a non-monotonic change in resonance frequency as a function of increasing encapsulation thickness due to the competing effects of added mass and increased stiffness. The performance of PMUT arrays is clearly influenced by the encapsulation. For certain array designs, the encapsulation significantly improved the arrays’ pressure output, a change that is attributed to the change in the acoustic wavelength and inter-element coupling. These findings highlight the impact of encapsulation in modifying and potentially enhancing PMUT performance.

Electrochemical impedance spectroscopy (EIS) has been established as an effective technique for bacterial biofilm detection. Through the need for miniaturization, the application of novel electrode materials gains interest. In this study, we introduce Sputtered IRidium Oxide Film (SIROF) electrodes of varying sizes and geometries as sensors for biofilm detection. Pre-emptive cyclic voltammetry (pre-cycling) was used to transform as-sputtered anhydrous iridium oxide films into hydroxides, reducing the impedance and allowing the material to be adopted for miniaturized biofilm sensors. Our investigation showed that especially lower scan rates during this pre-cycling process reduced the interfacial impedance, hence optimizing electrode performance for this application. Using EIS in combination with pre-cycled SIROF electrodes, we detected biofilm growth within 24 hours and successfully distinguished between biofilms of S. aureus and P. aeruginosa . Additionally, we analyzed the influence of electrode size on biofilm detection and characterization. This study highlights SIROF electrodes as a promising platform for sensitive and scalable biofilm monitoring.

This study reports on the encapsulation of piezoelectric micromachined ultrasonic transducer (PMUT) devices by hermetic Parylene F-VT4 (PVT4) and multilayer stacks of PVT4 combined with atomic layer deposition films. These encapsulations are evaluated for their potential to enable implantable PMUT devices for biomedical applications, providing necessary protection for both the device and the patient while preserving device performance. The mechanical and acoustic properties of coated and uncoated single PMUTs and 64x64 PMUT arrays were characterized in water. Results indicate that the resonance frequencies of both the single elements and the arrays change non-monotonically with increasing PVT4 thickness due to alterations in the equivalent mechanical properties of the composite membrane. While single PMUTs exhibited a monotonic decrease in displacement, encapsulation significantly improved the array's pressure output, attributed to changes in acoustic wavelength and inter-element coupling. This enhancement underscores the effectiveness of encapsulation in optimizing overall performance.

Compound nerve action potentials (CNAPs) were used as a metric to assess the stimulation performance of a novel high-density, transverse, intrafascicular electrode in rat models. We show characteristic CNAPs recorded from distally implanted cuff electrodes. Evaluation of the CNAPs as a function of stimulus current and calculation of recruitment plots were used to obtain a qualitative approximation of the neural interface’s placement and orientation inside the nerve. This method avoids elaborate surgeries required for the implantation of EMG electrodes and thus minimizes surgical complications and may accelerate the healing process of the implanted subject.

This work presents the broadband characterization of the electrical properties up to 110 GHz of a polymer before and after high temperature storage reliability stresses in the presence and absence of a thin inorganic capping layer. The latter is made of successive layers of HfO2, Al2O3, and HfO2 for a total thickness of 45 nm. The measurement results show that in the presence of the protective capping layer, the electrical properties of the polymer are stable with less than 1 % and 7.5 % variation after 1000 hours of HTS stress for the relative permittivity and loss tangent, respectively. For the unprotected polymer, variations of 2.3 % and 32 % are observed for the relative permittivity and the loss tangent, respectively.

There is an increasing interest in atomic layer deposition (ALD) on polymers for the development of membranes, electronics, (3D) nanostructures and specially for the development of hermetic packaging of the new generation of flexible implantable micro-devices. This evolution demands a better understanding of the ALD nucleation process on polymers, which has not been reported in a visual way. Herein, a visual study of ALD nucleation on polymers is presented, based on the different dry etching speeds between polymers (fast) and metal oxides (slow). An etching process removes the polyimide with the nucleating ALD acting as a mask, making the nucleation features visible through secondary electron microscopy analyses. The nucleation of both Al2O3 and HfO2 on polyimide was investigated. Both materials followed an island-coalescence nucleation. First, local islands formed, progressively coalescing into filaments, which connected and formed meshes. These meshes evolved into porous layers that eventually grew to a full layer, marking the end of the nucleation. Cross-sections were analyzed, observing no sub-surface growth. This approach was used to evaluate the influence of plasma-activating polyimide on the nucleation. Plasma-induced oxygen functionalities provided additional surface reactive sites for the ALD precursors to adsorb and start the nucleation. The presented nucleation study proved to be a straightforward and simple way to evaluate ALD nucleation on polymers.

The use of electronic microsystems as medical implants gains interests due to the combination of superior device functionality with extreme miniaturization. Electronic devices are not biocompatible and will suffer from corrosion, hence a very good hermetic device encapsulation is of utmost importance. The hermetic sealing of implantable electronics requires extremely good bi-directional barrier properties against diffusion of water, ions and gases. Moreover, extremely long biostability against body fluids and biomolecules is an important requirement for the barrier materials. In this work, an ALD multilayer of AlOx and HfOx in combination with flexible polyimide is used as a flexible hermetic encapsulation of an electronic CMOS chip which serves as an implantable probe (so called hd TIME (active high-density transverse intrafascicular microelectrode) probe) for neural recording and stimulation [1]. The main part consists of a 35μm thin CMOS chips with electrodes on top encapsulated with alternating layers of spin coated polyimide (PI2611) and biocompatible ALD layers. The total encapsulation is developed to provide excellent barrier properties. Each ALD stack (ALD-3) consists of AlOx (20 nm) capped on both sides with HfOx (8 nm) to avoid hydrolysis of AlOx. The ALD deposition temperature is 250°C. Special attention is payed to the adhesion of the ALD layers toward polyimide and vice versa. 3 to 4 PI/ALD-3 dyads are used for the total encapsulation, since long term implantation of the medical device is envisaged. Testing however is done using only a part of the total encapsulation, in order to enable to learn about the barrier properties in a reasonnable timeframe. The WVTR of a PI/ALD-3/PI film reached a value of 2.1 10-5 g/m2day (38°C and 100% RH), the total encapsulation with 3 to 4 dyads will lead to WVTR’s in the order of 10-6g/m2day. The same PI/ALD-3/PI film has been deposited on structured copper meanders and is exposed to PBS at 60°C for 3.5 years (equivalent to 17.5 years at 37°C) [2]. Up till now, no change in Cu resistivity has been observed proving the excellent barrier properties of the PI/ALD-3/PI film. [1] Rik Verplancke et al., 2020 J. Micromech. Microeng., 30, 015010 [2] Changzheng Li et al. 2019 Coatings, 9, 579

Barrier layers for the long-term encapsulation of implantable medical devices play a crucial role in the devices’ performance and reliability. Typically, to understand the stability and predict the lifetime of barriers (therefore, the implantable devices), the device is subjected to accelerated testing at higher temperatures compared to its service parameters. Nevertheless, at high temperatures, reaction and degradation mechanisms might be different, resulting in false accelerated test results. In this study, the maximum valid temperatures for the accelerated testing of two barrier layers were investigated: atomic layer deposited (ALD) Al2O3 and stacked ALD HfO2/Al2O3/HfO2, hereinafter referred to as ALD-3. The in-house developed standard barrier performance test is based on continuous electrical resistance monitoring and microscopic inspection of Cu patterns covered with the barrier and immersed in phosphate buffered saline (PBS) at temperatures up to 95 °C. The results demonstrate the valid temperature window to perform temperature acceleration tests. In addition, the optimized ALD layer in combination with polyimide (polyimide/ALD-3/polyimide) works as effective barrier at 60 °C for 1215 days, suggesting the potential applicability to the encapsulation of long-term implants.

Biocompatible BPA-PPD polyimide is widely used in the packaging of implantable devices. Plasma activation can improve its interaction with the surrounding tissue upon implantation. The influence of He, air, N2 and Ar plasma activation on polyimide's surface hydrophilicity, roughness, topography, composition and cell-surface interaction was evaluated, along with the influence of hydrophobic recovery on such properties. All plasma activations increased the surface hydrophilicity but neither the roughness nor topography changed. The increase was attributed to the incorporated O- and N-functionalities. 24 h after the activations the surface hydrophilicity decreased while maintaining the functionalities, due to the functionalities’ reorientation/migration towards the bulk of polyimide. Air and N2 activations improved the cell-surface interactions with fibroblasts. These were equally influenced by the surface hydrophilicity and the surface functionalities availability. The hydrophobic recovery lowered the initial cell adhesion but not the cell proliferation, as the hydrophobic recovery was progressively reversed in the culture media.

In recent years, there has been an increased interest in soft packaging for non-rigid medical implants. A promising technique to realize reliable soft packaging involves the inclusion of thin layers of atomic layer deposited (ALD) ceramics between biocompatible polymer layers. Crucial requirements are that those ALD layers are biocompatible and pinhole free to prevent unwanted interactions between the implant and the human body. In this research, a biocompatible thermally deposited 20 nm thick Al2O3-ALD layer is investigated for porosity by using three different techniques: copper electroplating, copper wet etching and linear sweep voltammetry (LSV). The porosity values obtained with the copper electroplating and copper wet etching techniques are comparable with one another (3.14 x 10(-6)%-3.18 x 10(-7)%) but are four to five orders of magnitude smaller than the porosity estimation obtained by the LSV test (8.04 x 10(-2)%-3.23 x 10(-3)%). This divergence in porosity is explained by two different contributions leading to an overestimation of pinhole density obtained through LSV. The destructive character of the LSV technique during which additional current contributions arise from copper corrosion and pinhole enlargement is identified as a first factor contributing to an overestimation of pinhole distribution. A second contribution arises from Poole-Frenkel emission and trap-assisted tunneling through the insulating Al2O3-ALD layer. As a consequence, LSV does not only detect pinholes but also single point defects, cluster defects and sealed line defects originating from unreacted OH ligands during ALD deposition. Based on those findings it was concluded that copper wet etching is the preferred method to be used in pinhole detection.

Within our internal FITEP technology platform (FITEP: Flexible Implantable Thin Electronic Package), a novel implantable packaging technology is under development in order to realize a very small, flexible, biomimetic package for electronic implants. This new platform enables a radical miniaturization of the final implanted device, which opens many new possibilities for the medical world, since it will be possible to insert electronic sensors in very small locations, such as arteries, nerves, glands,... The device encapsulation consists of a multilayer of biocompatible polymers and ultrathin ceramic diffusion barriers deposited using ALD techniques (ALD: atomic layer deposition) in order to fabricate a very thin and flexible but also highly hermetic device packaging. Concerning the selection of biocompatible polymers, polyimide can offer a profound mechanical support for the various device components, while Parylene with its excellent step coverage creates a highly conformal coating surrounding all components. Hermeticity can be realized by the use of ultrathin ceramic ALD layers such as Al2O3 and HfO2. An optimized ALD process will result in layers from very high quality with very good step coverage. As such, selected ALD layers of only a few tens of nm thick, can exhibit very low Water Vapor Transmission Rates (WVTR), making these ALD materials ideal as ultrathin diffusion barriers. The tested polyimide/ALD stack proved to be a very hermetic enclosure: copper patterns protected with the polyimide/ALD stack are still in perfect condition after more than 2 years of immersion in saline at 60 °C (test is still ongoing), while Cu patterns protected by the polyimide stack without ALD barriers showed first signs of damage already after 6 weeks exposure to saline. Platinum and gold are best suited for metallization of implanted electronics, but these noble metals do not adhere easily to polymers, hence dedicated measures to promote metal-polymer adhesion are essential. The FITEP platform is applied on a Si-probe for implantation in the peripheral nerves, consisting of a CMOS chip with recording and stimulation electrodes [Op de Beeck, M. 2017]. The chip is thinned down to 35um and packaged using polyimide and ALD multi-stacks, resulting in a 75um thin fully encapsulated chip, optimized to reduce the Foreign Body Reaction to obtain optimum electrode-nerve contact. Flexible interconnects are fabricated using gold and platinum sandwiched between polymers and ALD layers. For optimal charge injection, iridium oxide is used as electrode material. After this hermetic FITEP-based chip encapsulation, the CMOS chip is still fully functional, which was tested dry (in air) as well as during submersion in saline. First acute in vivo stimulation tests have shown good electrode stimulation capabilities. Mechanical bending tests on long 5um thick gold interconnects are performed, showing that even after up to 1.5 million bending cycles, no cracks occurred in the gold patterns (testing in air). Longer term immersion in saline and in-vivo testing showed some problems related to loss of adhesion and to galvanic effects of the metallization. These observations were leading to some improvements in the fabrication of the encapsulation. In a second packaging iteration of the CMOS chip, these improvements were realized and a new series of encapsulated devices is fabricated. First results are promising, showing improved metal adhesion. Longer term stability tests are on its way.

Long-term packaging of miniaturized, flexible implantable medical devices is essential for the next generation of medical devices. Polymer materials that are biocompatible and flexible have attracted extensive interest for the packaging of implantable medical devices, however realizing these devices with long-term hermeticity up to several years remains a great challenge. Here, polyimide (PI) based hermetic encapsulation was greatly improved by atomic layer deposition (ALD) of a nanoscale-thin, biocompatible sandwich stack of HfO2/Al2O3/HfO2 (ALD-3) between two polyimide layers. A thin copper film covered with a PI/ALD-3/PI barrier maintained excellent electrochemical performance over 1028 days (2.8 years) during acceleration tests at 60 °C in phosphate buffered saline solution (PBS). This stability is equivalent to approximately 14 years at 37 °C. The coatings were monitored in situ through electrochemical impedance spectroscopy (EIS), were inspected by microscope, and were further analyzed using equivalent circuit modeling. The failure mode of ALD Al2O3, ALD-3, and PI soaking in PBS is discussed. Encapsulation using ultrathin ALD-3 combined with PI for the packaging of implantable medical devices is robust at the acceleration temperature condition for more than 2.8 years, showing that it has great potential as reliable packaging for long-term implantable devices.

In this work, the development of an active high-density transverse intrafascicular micro-electrode (hd-TIME) probe to interface with the peripheral nervous system is presented. The TIME approach is combined with an active probe chip, resulting in improved selectivity and excellent signal-to-noise ratio. The integrated multiplexing capabilities reduce the number of external electrical connections and facilitate the positioning of the probe during implantation, as the most interesting electrodes of the electrode array can be selected after implantation. The probe chip is packaged using thin-film manufacturing techniques to allow for a minimally invasive electronic package. Special attention is paid to the miniaturization, the mechanical flexibility and the hermetic encapsulation of the device. A customized probe chip was designed and packaged using a flexible, implantable thin electronic package (FITEP) process platform. The platform is specifically developed for making slim, ultra-compliant, implantable complementary metal-oxide-semiconductor based electronic devices. Multilayer stacks of polyimide films and HfO2/Al2O3/HfO2 layers deposited via atomic layer deposition act as bidirectional diffusion barriers and are key to the hermetic encapsulation. Their efficacy was demonstrated both by water vapor transmission rate tests and accelerated immersion tests in phosphate buffered saline at 60 degrees C. Using the hd-TIME probe, an innovative implantation method is developed to prevent the fascicles from moving away when the epineurium is pierced. In addition, by transversally implanting the hd-TIME probe in the proximal sciatic nerve of a rat, selective activation within the nerve was demonstrated. The FITEP process platform can be applied to a broader range of integrated circuits and can be considered as an enabler for other biomedical applications.

Advanced bionic prosthetics that can restore both the motor functionality and sensory perception of an amputee, require high-resolution recording and stimulation interfaces targeting the peripheral nervous system (PNS). To provide high nerve fiber selectivity, we propose a low-noise (3.67 mu Vrms), low-power (2.24mW) and high-density CMOS microelectrode probe for intra-neural implantation. The probe is composed of two ICs, encapsulated in a biocompatible and hermetic package, each featuring 64 recording and 16 stimulation electrodes. A backend IC digitizes the recorded signals at 31.25kS/s and provides spike detection.

To realize optimal recording and stimulation of peripheral nerve cells, a CMOS chip is made with a multitude of electrodes which can be individually addressed in order to select after implantation the 16 best positioned electrodes. Since the Foreign Body Reaction should be minimal for optimum electrode-nerve contact, the CMOS chip is thinned down to 35um and fully packaged resulting in a 75um thin encapsulated chip. The chip is embedded in a biocompatible stack consisting of polymers and inorganic diffusion barriers deposited using atomic layer deposition (ALD). A biocompatible metallization is realized using gold and platinum sandwiched between polymers and ALD layers for flexible interconnects, and iridium oxide (IrOx) is selected as electrode material for optimal charge injection during stimulation. After this dedicated packaging based on the FITEP technology platform (Flexible Implantable Thin Electronic Package), the CMOS chip is still fully functional, which was tested dry (in air) as well as during submersion in saline. The form factor of the packaged chip is optimized for intra-fascicular implantation with minimum tissue damage. First acute in vivo stimulation tests proved that the stimulation capabilities of the IrOx electrodes are very good.