Robot and Servo Drive Lab.
Packaging of Bio-MEMS: Strategies, Technologies,
and Applications
IEEE TRANSACTIONS ON ADVANCED PACKAGING, VOL. 28, NO. 4,
NOVEMBER 2005
Thomas Velten, Hans Heinrich Ruf, David Barrow, Nikos Aspragathos,
Panagiotis Lazarou, Erik Jung, Chantal Khan Malek, Martin Richter,
Jürgen Kruckow, Martin Wackerle
Professor: Ming-Shyan Wang
Student: Ju-Yi Kuo
Department of Electrical Engineering
Southern Taiwan University of Science and Technology
2016/7/13
Outline
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Introduction
STRATEGIES, TECHNOLOGIES, AND APPLICATIONS
CONCLUSION
ACKNOWLEDGMENT
References
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Abstract
Biomicroelectromechanical systems (bio-MEMS) are MEMS which are
designed for medical or biological applications. As with other MEMS, bioMEMS frequently, have to be packaged to provide an interface to the
macroscale world of the user. Bio-MEMS can be roughly divided in two
groups. Bio-MEMS can be pure technical systems applied in a biological
environment or technical systems which integrate biological materials as one
functional component of the system. In both cases, the materials which have
intimate contact to biological matter have to be biocompatible to avoid
unintentional effects on the biological substances, which in case of medical
implants, could harm the patient. In the case of biosensors, the use of
nonbiocompatible materials could interfere with the biological subcomponents
which would affect the sensor’s performance. Bio-MEMS containing biological
subcomponents require the use of “biocompatible” technologies for assembly
and packaging; e.g., high temperatures occurring, for instance, during
thermosonic wire bonding and other thermobonding processes would denature
the bioaffinity layers on biosensor chips. This means that the use of selected or
alternative packaging and assembly methods, or new strategies, is necessary
for a wide range of bio-MEMS applications. This paper provides an overview
2016/7/13 of some of the strategies, technologies, and applications in the field of bioMEMS
packaging.
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Introduction
MEMS for biological or medical applications or involving biological
component(s), so-called biomicroelectromechanical systems (bio-MEMS)
[1] are becoming more and more popular. Depending on their applications,
this is justified by the inherent benefits of miniaturization in bio-MEMS
such as small size, low weight, potential low unit costs per device, efficient
transduction processes, high reaction rate, low reagent consumption, and
the potential to manufacture minimally invasive devices and systems. A
prominent medical application for bio-MEMS is the field of medical
implants such as pacemakers, hearing aids and drugeluting implants to
name a few. It is obvious that miniaturization is a key desirable
requirement for implantable devices. This is especially true for implants in
very small organs or those which are inserted using minimally invasive
surgical procedures where the maximum allowable size is restricted by the
diameter of the working channel in an endoscope.
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Medical implants are often rather complex systems and can consist of many
components such as power sources, transducers, control units, modules for wireless
communication, etc., potentially resulting in rather bulky devices if inappropriate
packaging technologies are used. Example packaging technologies suitable for
miniaturized and high-density bio-MEMS includes bare die assembly techniques
like flip-chip technology. These, provide thin, small, and lightweight features and
can be implemented on a multitude of substrates such as ceramic, laminate, molded
interconnect devices (MID) as well as on flexible substrates. Very often, these
processes use materials which are not biocompatible. In this case, additional
encapsulation steps are necessary to avoid a direct contact between
nonbiocompatible materials and body fluids or tissue.
Another bio-MEMS category comprises biosensors or complete lab-on-a-chip
systems for analytical tasks [2]. Biochips and biosensors are regarded as key
elements for the development of multianalyte detecting instruments, especially of
hand-held instruments for point-of-care or point-of-use testing.
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STRATEGIES, TECHNOLOGIES,
AND APPLICATIONS
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A. Bio-MEMS Subsystems Partitioning Strategies
1) Material Trends: Bio-MEMS defines a diversity of microsystems functional embodiments.
This diversity continues to expand as applications in different industrial sectors are
developed [1]. One important domain of these developments is led by the miniaturization of
systems for (bio)chemical and molecular analysis/synthesis [2]. This is driven by manifold
reasons such as mass, volume, performance, and ergonomics considerations. Such
multifunctional devices and systems may incorporate (bio)chemical, biological,
electromagnetic, electronic, fluidic, and mechanical functionalities. Furthermore, they are
truly three-dimensional (3-D), micro- and nanostructured and moving toward reconfigurable
capability. Accordingly, to meet these diverse functions, fabrication materials are diverse,
including polymers [3], diamond [4], metals [5], silicon [6], ceramics, glass [7], and
hydrogels [8]. These materials are used as such but also in combination with selective
surface customizations and coatings [9]. This move toward the use of nonsilicon matrices,
particularly polymers, [10] has become particularly evident, and is driven by a combination
of unit-cost manufacturing criteria and functional requirements (e.g., piezoelectric actuation,
optical interconnection) that cannot be met by the use of silicon.
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2) Product Manufacturing Considerations: A principal technical challenge for the
manufacturing of a system which is in part, or wholly, constructed of
microcomponents is a generic and coherent strategy for integration including
packaging. How this applies to products varies enormously as might be seen from
two example broad product categories:
Integrated Chemical Anaysis Microsystem (uTAS)
Massively Parallel Biochemicals Synthesiser (uPLANT)
3) Modularity: Since the early conceptualization of microsystems with chemicals
functionality [2], [11], contrasting approaches have been taken for the integration of
miniaturized systems ranging from whole wafer [12] to modular configurations in
two-dimensional (2-D) [13]–[15] and 3-D stacked [16], [17] formats. However, few
of these earlier examples demonstrated the space-saving features that are
characteristic of, for example, chip scale packaging (such as in SHELLCASE— see
www.shellcase.com) with the consequence that assemblages of microcomponents
became disproportionately large “miniature” systems. For some very large specific
product markets.
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4) New Enabling Processes: New materials and processing techniques are required
that can more readily accommodate the integration and packaging of
environmentally sensitive materials such as biomolecules, organelles, and cells
within microdevices and integrated microsystems. For instance, bioerodible
polymers [18] are a class of materials that present new opportunities as a
constructional material for biocompatible implantable microdevices (e.g., drugeluting stents) or package coating for temporarily implanted microsystems. The use
of extremely short pulse lasers to substractively machine bioerodible polymers may
be profitably extended to polymers which incorporate “active” ingredients. Low
fluence conditions with short pulsewidth determines a very shallow damage zone
[19] beyond which active ingredients may survive the machining process. Equally,
advances in printing technology [20] and electrospray [21] are being explored as a
“soft” process for the 2-D and 3-D overlay deposition of biomolecules such as
peptides, growth factors, and biointerface coatings on microstructures. Such
ballistic additive processes provide elegant, rapid, and dynamically programmable
alternatives to traditional subtractive processes which frequently damage biological
materials. New post-assembly processing techniques for incorporating biological
materials [22] and synthetic molecular receptors [23] may also influence
2016/7/13subsystems packaging strategies and shift an emphasis to monolithically integrated
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systems.
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B. Methods for Microassembly of Bio-MEMS
Bio-MEMS very often consist of a combination of sensors, actuators, processing, and
communication circuits. Examples of such systems include miniature biochemical reaction
chambers, lab-on-a-chip devices and systems, and micropumps. Various microfabrication
methods that originate from the microelectronics industry, such as photolithography, UV
Laser micromachining, and polymer embossing, have been developed to produce bioMEMS microparts. As the complete products are often comprised of components with
mechanical moving parts (microvalves, micropumps, microreservoirs), microassembly
processes are required. Microassembly is the discipline of positioning, orientating, and
assembling of micrometer-scale components into complex microsystems. The general goal
is to achieve hybrid microscale devices and systems of high complexity, while maintaining
high yield and lowcost. So far, currentbio-MEMS assembling techniques follow the “pickand-place” approach, i.e., all components are assembled in one lengthy sequential process.
This ultimately affects the cost of the microassembly process, raising it to more than 50%
of the overall product cost [24]. An excellent paper that describes in detail MEMS
manufacturing and microassembly issues is [25].
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Automatic microassembly machines and robotic manipulation are also considered
as solutions. Zhou et al. [26] successfully managed to combine vision and force
sensors. The vision system provided feedback on the relative placement of parts
over large ranges. A novel force sensor provided extremely precise feedback on the
interactions among microparts as contact occurs. This strategy of combining visual
and force feedback can be incorporated in automated microassembly machines or
common pick-and-place systems, thus enhancing their efficiency and ability of
performing more complex microassembly and packaging operations.
Microassembly with robots requires extreme accuracy and precision. Typical
robotic microassembly systems rely on the use of microgrippers for the
manipulation of objects. There are various types of grippers proposed for physical
contact manipulation (mechanical, thermal, electrostatic, piezoelectric, adhesive,
vacuum). As an alternative, Fatikow et al. [27] proposed an assembly system with
microrobots based on piezoelectric legs and equipped with a 3 Degree of Freedom
(3DOF) gripper. A vision system provided a constant feedback of their position and
orientation. A fuzzy controller evaluated the data and decided on the desirable
behavior and movement of each robot. The advantage of this system lies in its
flexibility, since different robot types can operate simultaneously by performing
2016/7/13different tasks.
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C. Technologies for Joining Polymer Bio-MEMS Components
Polymer substrates have attracted great interest, particularly for life science
applications and especially for low-cost and disposable devices. They require
joining processes that are different from those developed for silicon or glass-based
devices [35], [36]; in particular low-temperature bonding processes that do not
necessitate the application of voltage, high pressure, or vacuum. In most cases,
polymer microfluidic devices are sealed by adhesive joining [37]. Other techniques
[38] such as lamination, direct and indirect (such as ultrasonic) thermal welding,
solvent welding (in liquid or vapor phase), thermal bonding, and plasma bonding
have been adapted to some extent to the need of polymeric microcomponents. New
processes have also been developed for meeting their specific requirements [39],
[40].
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D. Packaging of Miniature Medical Devices
In medical applications, miniaturization is key for implantable devices. Here, bare
die assembly techniques like flipchip technology are the preferred choice, as they
provide thin, small, and lightweight features and can be assembled on ceramic,
laminate, MID molded, and flexible substrates. Flip-chip technology can substitute
and complement conventional surface-mounted devices (SMD) or wire bonding
processes for an even higher degree of miniaturization. The variety of technologies
for those processes ranging from soldering to adhesive bonding offers solutions for
a wide diversity of applications.The devices in which most advanced processes are
being used are permanent implants such as pacemakers or eye pressure implants.
New developments like brain implants for permanent monitoring or treatment (e.g.,
epilepsy) are also close to approval. Future developments will include concealed
monitoring devices (e.g., sensor band aids or sensor-shirts) where microelectronic
devices are integrated in clothing, closing the gap between medical
therapy/diagnosis in the hospital and the ubiquitous monitoring of patients with a
risk factor, as part of their everyday life.
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A crucial development in order to maximize these goals has been the development
of ultrathin silicon devices as well as rerouting techniques to enable high-volume,
low-cost manufacturing. The capability to fabricate thin integrated circuits (Ics) to
less than 50 m thickness, thereby minimizing the total height of the assembly to a
mere breadth of a human hair, is the enabling technology for flat and flexible
systems. Also, respective interconnect techniques are required in order to maintain
these ideal properties (Fig. 1).
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When ultrathin chips are not an option, the use of standard thickness chips can still
enable extremely small devices by the use of flip-chip technology. Hearing aids are
an excellent example which demonstrates the evolution from large boxes worn
around the neck, to those now small enough to incorporate highperformance digital
signal processor (DSP), microcontrollers, microphones, and batteries in one tiny inthe-ear device (Fig. 2).
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In order to increase the functionality per
unit volume and simultaneously keep a
given process flow (such as surfacemount technology (SMT)) the mounting,
of bare die chips in an SMDcompatible
form factor is possible. Sometimes
termed chip scale packages (CSP), these
can be mounted together with other
SMD components in a high-volume
capable process [96] without the need
for special high-precision bonding
equipment and/or ultrafine- line
substrate technology. Examples here are
pacemaker or defibrillator units, which
employ digital and analog highperformance chips, which in a packaged
or wire-bonded format would require
significantly more space and weight
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(Fig. 3).
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An even more nonconventional
understanding of system integration is
given by the evolution of textiles and
their ability to serve as substrates for
electronic mounting. Although today’s
scenarios are tested for sports and
comfort, future concepts will well
employ this integration also for home
care or hospital monitoring. Direct
assembly of microelectronic and sensor
devices to, e.g., a T-shirt or a bed sheet,
may allow much less intrusive forms of
diagnosis and status tracking. Fig. 5
shows an example of an integrated
electrocardiogr aphic (EKG) sensor into a
worn T-shirt. The cables are currently
required only to verify the performance
against a metallic thread woven into the
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fabric of the textile.
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CONCLUSION
Packaging of bio-MEMS plays an important role in providing bio-MEMS with an
interface to the macroworld of the user. Many of the employed packaging methods
stem from the packaging of nonbio-MEMS and have been adapted to biological or
medical requirements. A new trend of using polymer bio-MEMS, mainly because
of perceived economic reasons, has become evident. Many of the techniques known
from packaging silicon-based MEMS cannot be applied to polymer bio-MEMS. In
this paper, conventional packaging technologies, as well as novel technologies
especially developed for polymer MEMS, have been presented. Considerations on
strategies for partitioning subsystems within integrated subsystems have also been
presented. These strategies strongly influence the number of packaging steps
necessary for assembling the whole system and, thus, influence the costs of
manufacture in which the packaging costs account for a very significant
component. Several approaches for microassembly of hybrid microscale devices
have been presented. These all aim to provide a means for the rapid, simple, and
reliable positioning, orientating, and assembling of microcomponents into complex
microsystems in order to enable a high-yield and throughput by unit reduction of
microassembly costs.
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Special applications of bio-MEMS packaging such as packaging of a micropump
for biological applications and packaging of a biosensor for analytical tasks have
been presented. Within the packaged micropump, the fluid contacts only with three
materials:
1) silicon, 2) the plastics of the housing, and 3) one glue between the housing and
chip, to be selected depending on the requirements of the application. With that,
this micropump can be used in various bio-MEMS applications. The presented
BIOMIC biosensor was packaged to enable an early practical evaluation in the
product development process which is an important asset in rapid product
development. The relatively low yield of commercial biosensor developments can
be attributed to a lack of feasible, functional, and economic packaging technology
which hampers the transformation of a scientific biosensor into a commercial
device. The selection of technologies for prototyping is also an important economic
factor since the transformation mentioned above requires the major portion of the
development costs.
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It is important to note the interdependence of the various microfabrication
and assembly processes in the packaging chain. The chip layout design
with the clearly separated functional domains, for instance, was a good
basis for the chosen packaging techniques. It is clear that biochip design,
fabrication, and packaging should be implemented as an integrated process.
The examples presented for the packaging of bio-MEMS demonstrate that
the choice of materials and processes for packaging are much more
stringent for bio-MEMS than for pure technical MEMS. The same applies
in some cases to the required density of packaging. An example are tiny
medical implants. Here, the costs are less important than the size with the
consequence that the most sophisticated packaging techniques can be
applied.
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ACKNOWLEDGMENT
T. Velten and H. Ruf would like to thank the other partners in the BIOMIC
consortium for their fruitful and enjoyable collaboration. H. Ruf would also like to
thank L. B. Larsen, from Nunc, Roskilde, Denmark, as well as M. Denninger and
R. Haupt, from SMB, Lyngby, Denmark, for fabricating the microfluidic module
and performing the underfill gluing of this module. He would also like to thank K.
Misiakos from the Institute of Microelectronics/National Center for Scientific
Research “DEMOKRITOS,” Greece, who developed the BIOMIC biosensor chip
and who provided drawings of this chip. C. K. Malek would like to thank both Dr.
R. Truckenmüller from the Institut für Mikrostrukturtechnik, Forschungszentrum
Karlsruhe GmbH, for providing valuable materials and comments and Prof. O.
Geschke, Mikroelektronik Centret (MIC), Technical University of Denmark, for
helpful comments on bonding polymers. The authors would also like to thank S.
Taylor of Cardiff University for the helpful manuscript revisions. Also, the writing
of this review article was carried out within the framework of the EC Network of
Excellence “Multi-Material Micro Manufacture: Technologies and Applications
(4M).”
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[1] R. Bashir, “BioMEMS: State-of-the-art in detection, opportunities and prospects,” Adv.
Drug Delivery Rev., vol. 56, pp. 1565–1586, 2004.
[2] A. Manz et al., “Miniaturized total chemical analysis systems. A novel concept for
chemical sensing,” Sens. Actuators B, Chem.,vol. B1, pp. 249–255, 1990.
[3] H. Becker et al., “Polymer microfluidic devices,” Talanta, vol. 56, pp.267–287, 2002.
[4] S. Guillaudeu et al., “Fabrication of 2-m-wide poly-crystalline diamond channels using
silicon molds for micro-fluidic applications,” Diamond Rel. Mater. , vol. 12, pp. 65–69, 2003.
[5] G. Kotzar et al., “Evaluation of MEMS materials of construction for implantable medical
devices,” Biomater., vol. 23, pp. 2737–2750, 2002.
[6] R. S. Shawgo et al., “BioMEMS for drug delivery,” Current Opinion Solid-State Mater.
Sci., vol. 6, pp. 329–334, 2004.
[7] K. Lee and L. Lin, “Surface micromachined glass and polysilicon microchannels using
MUMP’s for BioMEMS applications,” Sens. Actuators A, Phys., vol. 111, pp. 44–50, 2004.
Department of Electrical Engineering
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Thanks for listening
2016/7/13
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