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Recent Advances in Implantable Medical Systems with Highly-Heterogeneous

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 Recent Advances in Implantable Medical Systems with Highly-Heterogeneous Integration
Abdulhameed Abdal, Akeeb Hassan, and P. Markondeya Raj
Dept. of Biomedical Engineering, College of Engineering and Computing
Florida International University, Miami, FL 33174, USA
Email: aabdal@fiu.edu; ahass050@fiu.edu; mpulugur@fiu.edu

Abstract: Future implantable biomedical systems will factor for implantable biomedical systems is to be
require power and data telemetry with multiferroic hermetic in aqueous and reactive aging conditions.
interfaces, signal modulation, low-impedance Hermeticity protects the electronic system from water
electrodes with high current injection, remateable and reactive chemicals in the target tissue
connectors - all in a highly miniaturized form-factor environment. Furthermore, cardiac pacemakers,
with reliability in a reactive aqueous environment. neural recording systems and neural stimulators also
They provide a combination of functions such as need to provide remateability in a surgical
neural recording and stimulation, imaging, environment. Addressing remateability in electronic
spectroscopy, electrochemical sensing and others. packaging would benefit surgeons to troubleshoot
They, thus, drive the most advanced heterogeneous failed components and allows minimal intervention to
integration. Advancing system components and their disassemble and reassemble the system.
3D connectivity in small form-factors are both
critical to realize such future medical implants. The Because of the reliability constraints and long R&D
system components are advanced through innovative cycle time to qualify new technologies, implantable
nanomaterials, multiphysics-based material designs medical products tend to utilize pre-approved or
to achieve the performance metrics, and hybrid established materials and technologies for shorter time
additive and semi-additive manufacturing to clinical use, while customizing the design and
technologies. The integration technologies rely on integration advances with power sources, electrode or
advanced chiplet fan-out embedding technologies in sensing interfaces to the specific application. In typical
flexible or rigid-flex substrates that provide seamless implantable technologies, the primary electronics
but reliable interconnect technologies between the package is sealed in a titanium case with ceramic
system components. This article will briefly review feedthroughs, with PtIr wire electrodes of high
some of the key functional packaging build blocks strength and reliability that extend to the target
towards these heterogeneous 3D implanted medical locations. For battery-driven, low-power applications
systems. that support few channels, low stimulation current,
low duty cycle and long-term applications such as
I. INTRODUCTION pacemakers, the 3D technologies within the titanium
include stacked ICs and packages for signal
Implantable biomedical systems represent the most conditioning and data processing, batteries, capacitors,
complex class of heterogeneous systems. They require power regulation and other functions. Key innovations
high functional densities in highly-miniaturized 3D are driven by this existing framework where the
packages, with thin form-factors that are determined titanium case supports a highly-integrated 3D
by physiological and surgical constraints, and electronics module.
reliability under aqueous and aggressive reactive
environments. The systems perform critical functions
such as neural recording and stimulation or condition-
monitoring through specific biomarkers. These
sensors utilize various other modalities such as
biophotonics through near-infrared or fluorescence
spectroscopy to detect the concentration of critical
biomarkers such as glucose, blood oxygenation for
hemodynamics or others and wirelessly communicate
to an external reader. This requires power and data
telemetry, sensing interfaces, and associated data Figure 1: Biomedical devices from titanium can with
modulation and conversion, all of which lead to the wired connectors, high-density feedthroughs with
most complex electronic function in a single titanium connected to flex, and miniaturized 3D
miniaturized package. The underlying heterogeneous packages extended to flex. [1]
integration technologies are dependent on the power For emerging higher-power density, but miniaturized
and data rates, size constraints, and process maturity systems such as those used in neuroprosthetics (ex:
for implantable medical devices. The most important retinal prosthetics, brain-machine interfaces), the
hermetic package supports dozens of feedthroughs, ultrasonic imaging systems are based on piezoelectric
titanium cap and gold braze to achieve higher arrays (256-512) that are 3D integrated with a flex
interconnect density to the external electrode array. using silicon interposers with through-vias to
The neural interfaces in this case are typically based underneath flex that support the signal processing
on microwire bundles, polymer flex electrodes or chips. Emerging 3D heterogeneously-integrated
vertical high-density pin electrode arrays. The trend of package architecture details of these systems are
Pt feedthroughs in thick-film alumina is now leading illustrated in Figure 2.
to ultraminiaturized glass or ceramic ribbon
feedthroughs that can achieve much higher Thin and flexible hermetic ribbon packages will have
interconnect or channel density with the flex electrode pervasive role in all future neuro, spectroscopic,
array without compromising reliability. This trend is imaging and multimodal sensing technologies.
illustrated in Figure 1, showing implantable systems However, present flex-packaging only focuses on
based on metal can with feedthroughs on the left, discrete and prepackaged components, limiting their
migrating to smaller geometries with planar or ability for integration in hermetic ribbons. Embedded
cylindrical geometries, and eventually to thin and fan-out interconnects with thin bare dies or their
electronic nodes or motes that are so miniaturized that sub-units such as chiplets will enable such hermetic
they are now being visualized as grains or dust. packages where the chiplets are embedded in the flex
core, and sandwiched between metal-ceramic ribbon
windows. Strength and handling are a major concern
at smaller thickness. Ultra-thin and ultra-tough
hermetic ribbons are the need of the future. These are
extended with low-electrical impedance and
mechanically-compliant nanoelectrodes for higher
sensitivity to low voltage neural signals and also to
inject higher current at lower voltages for stimulation.
The team at FIU are advancing such flex ribbon
packaging to not only include the signal processing
and photonic chips, but also with miniaturized high-
power-density modules, drivers and switches to
control the timing of the LEDs and integrate the
wireless sensing. This report highlights some of the
recent advances in implantable device packaging.

II. RECENT ADVANCES IN

IMPLANTABLE SYSTEM
BUILDING BLOCKS
Zero-power Passive Neural Recording: For neural
Figure 2: Spectrum of biomedical devices for health- recording, biosensing or other monitoring functions,
monitoring, imaging, spectroscopy and neural biomedical systems are going through major
recording. [Neuralink [2]; Camera pill [3]; Glucose innovations that are driven not only by advances in the
fluoroscence monitor [4], CardioMEMS pressure sensing interfaces but also through new simplified
sensing [5]; ultrasonic imaging Array [6]. signal conditioning and data telemetry topologies. In
the simplest architecture, a zero-power telemetry
More functional medical systems incorporate imaging
scheme is widely adapted to monitor neural activity at
with higher telemetry bandwidth. These are injected
critical areas. The incoming RF signal is backscattered
into the body as wireless camera pills or endoscopes
to carry the neural signal with it, which can be
or smart imaging catheters that can collect images,
demodulated through an external reader. The
process them and communicate them to outside. For
measured action potentials are wirelessly
such wireless imaging systems, the heterogeneously-
communicated through the backscattered RF signal
integrated 3D system is packaged into a cylindrical pill
that carries the sensing information, as shown in
with electromagnetically and optically-transparent
Figure 3. Such topologies do not need power telemetry
windows. The system components involve antenna
and rectification as the internal components do not
and RF transmitter on one end, lens + CMOS camera
need any DC bias, and are completely passive. FIU
+ ASIC on the other hand, with a battery in the middle.
has recently advanced such passive neural recording
This 3D package pill can communicate images to an
with thin flex substrates, as shown in Figure 3. With
external reader around the waist. Alternative
topology advances, continuous recording neural
potentials of 15-20 microvolts are now showing to be Hermetic feedthroughs: Ceramic-to-metal
feasible with this approach [7, 8]. feedthroughs are the universal “gold” standard in
implantable medical devices such as pacemakers and
Multiferroic power telemetry: For most wireless cochlear implants. Ceramic feedthroughs are stronger
sensing applications, the sensing signal needs to be and more reliable, enabling a key paradigm shift in
conditioned through analog and digital signal high-reliability packages. Through-glass via
processing chains, load modulation, timers and interposers (TGV) are being widely studied for high-
switches. All these need DC bias and hence a power bandwidth 2.5D interposers in high-performance
telemetry link with rectification is needed in all these computing. For biomedical implants, the via density is
cases. Therefore, one of the key features of not as high but need to be hermetic, with
implantable bioelectronics is wireless power biocompatible metals such as platinum, tungsten or
telemetry. Most batteryless implantable devices are others. The TGV interposer is manufactured from
based on magnetically-coupled coils referred to as high-quality borosilicate glass, fused silica, and
inductive links. These near-field links not only power sapphire to adhere to hermeticity and biocompatibility
the devices but also to modulate the load of an requirements. Schott Promoceler® designed a process
incoming RF signal and backscatter to provide the for glass-metal feedthroughs with high thermal
data. However, the receiving coils are usually limited expansion coefficient glass that enables it to firmly
in size because they are implanted in the human body, shrink onto the tungsten vias to create a hermetic seal,
which may affect the power transfer efficiency as the as illustrated in Figure 4. Hermiticity of 10-12 millibar
mutual coupling and Quality factor dramatically - liter/second was achieved. Glasses have ~10x higher
reduces with size. In order to achieve higher power compressive strength than its tensile strength. Bonding
transfer efficiency, new transduction mechanisms flex electrode arrays to the feedthrough pads is the
based on multiphysics phenomena such as piezo- next challenge.
magnetostrictive coupling is developed for telemetry
in unprecedented geometries of sub-mm dimensions.
Piezo-magnetostrictive power telemetry is
advantageous compared to pure piezoelectric power
delivery because it can be focused with magnetic
lenses better than ultrasonic power but also because
the maximum magnetic field power input inside the
body at low frequencies is 100 mW/mm2 as opposed
to ultrasonic power with 10X lower limits. Unlike
inductive link, the delivered power can retain high
power transfer efficiency even with smaller receiving
units. By utilizing piezo-magnetostrictive stacks as Figure 4: Evolution of feedthroughs from cofired
flexible films, power sources can be thus integrated in ceramic-platinum to glass feedthroughs, further aided
the flex package core. This approach is illustrated in by glass-to-glass seamless bonding [9, 10].
Figure 3 through a biophotonic package on
Metglas®/PVDF/Metglas® stack. Remateable Connectors: The need for remateable
interconnects increases as the complexity of
implantable systems escalates with higher electrodes
counts and connection nodes that extend to various
parts of the body under the associated physiological
constraints. The remateability feature provides the
ability to connect and disconnect different components
for troubleshooting, such as during component
failures, without the need for removing the whole
system. Universal requirements of remateable
interconnections can be defined in terms of
Figure 3: FIU’s advances in passive (zero-power) mechanical, electrical, thermal, material, and
neural recording (a). Leadframe molded diodes (not reliability performance. In terms of mechanical
shown) are assembled to complete the circuit. performance, insertion, extraction, and retention
Wireless biophotonic system with piezo- forces must be low while retaining low contact
magnetostrictive power telemetry inside the flex resistance. The prevalent remateable connectors are
carrier (b). based on linear array of axially-arranged pins with ring
contacts on the male side that are pressed against a
terminal spring contact on the female side. This Low-impedance Neural interfaces: The most
concept has been adopted in generations of prominent materials used in electrodes for neural
neuroimplants as a “gold” standard [11]. The recording and stimulation are linear wire arrays of Pt-
technology is advanced to utilize PtIr springs and gold Ir. These are proven for long-term use in peripheral
ring contacts to allow a linear array channel system nervous systems under complex physiological
with low retention and extraction forces on the environment where the wires are subjected to bending
compressible springs. The configuration allows self- and twisting loads. The impedance of the electrodes is
interlocking and provides a near-hermetic seal by largely determined by the area of exposure of the metal.
adding microscrews as redundancy. This trend is The high impedance of current electrode structures
illustrated in Figure 5. Remateable connectors are limits the selectivity of neural signal. Lowering the
further advanced by Jung et al. [12] to achieve a multi- impedance increases electrode sensitivity and increases
channel inline connector system that addresses the the electric change transfer during stimulation. Since
current limitations of inline connectors such as the increased surface area is directly related to lowering
expandability, contamination, and replaceable parts of impedance, nanostructured surfaces that can
caused by wear and tear. An innovative approach to increase the surface area without increasing the lateral
address this problem was demonstrated by FIU using electrode dimensions are utilized to improve signal
compressible and deformable z-elastomer interposers quality and miniaturize the electrodes for safer surgical
[13]. The designed test vehicles consisted of a z- procedures. Such electrodes should also be reliable
interposer in a flexible liquid crystal polymer (LCP) against mechanical loads and long-term chemical
substrate that can be interconnected with stability of surface without degradation. Porous
feedthroughs, all clamped together using microscrews platinum black coatings, activated iridium oxide, or
for a strong connection. Such flexible area-array gold pillars coated with PEDOT-PSS (poly(3,4-
remeatable interconnects are now being qualified for ethylenedioxythiophene – polystyrene sulphonate) are
hermiticity to achieve performance stability without emerging as candidates because of their
compromising the reliability of the interconnects. electrochemical, chemical and mechanical stability.
This trend is illustrated in Figure 6 through a material
. map where the current injection limit and the
normalized impedance are shown on each axis.. We
recently advanced this approach with biocompatible
porous metal wire electrodes of more than 100X
increase in area, leading to low-impedance interfaces.
These electrodes architectures with sintered nanometal
are readily compatible with existing PtIr microwire
arrays, resulting in faster time to clinical use with
minimal disruption to the product architecture.
Figure 5: Evolution of remeatable connectors for
implantable devices from linear spring-locked pins to
area-array connectors [14].
III. SUMMARY
Implantable biomedical implants drive the most
advanced heterogeneous integration technologies at
nanoscale with next-generation materials and
processes in order to improve functional density, and
reliability in the required form-factor. Key building
blocks in all these technologies involve high-density
feedthroughs, remateable connectors, hermetic sealing
and functional integration to advance sensing, power,
and data telemetry. This article highlights such key
building blocks. In the future, power sources,
photonics, analog signal chain, wireless
communication interfaces will be co-packaged by
Figure 6: Low-impedance electrodes with high surface embedding and fan-out interconnects, leading to high
area and high-current injection electrodes for performance with physiology-driven form-factors
neurostimulation and recording. Redrawn from [15]. through true heterogeneous system integration.
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