MEMS actuators for biomedical applications: A review

Abstract

Micro-electromechanical-system (MEMS) based actuators, which transduce certain domains of energy into mechanical movements in the microscopic scale, are increasingly contributing to the areas of biomedical engineering and healthcare applications. They are enabling new functionalities in biomedical devices through their unique miniaturized features. An effective selection of a particular actuator, among a wide range of actuator types available in the MEMS field, needs to be made through the assessment of many factors involved in both the actuator itself and the target application. This paper presents an overview of the state-of-the-art MEMS actuators that have been developed for biomedical applications. The actuation methods, working principle, and imperative features of these actuators are discussed along with their specific applications. An emphasis of this review is placed on temperature-responsive, electromagnetic, piezoelectric, and fluid-driven actuators towards various application areas including lab-on-a-chip, drug delivery systems, cardiac devices and surgical tools. It also highlights the key issues of MEMS actuators in light of biomedical applications.

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MEMS Actuators for Biomedical Applications: A Review
Farah Afiqa Mohd Ghazali1, Md. Nazibul Hasan1, Tariq Rehman1,2, Marwan Nafea3,
Mohamed Sultan Mohamed Ali1, and Kenichi Takahata4
1 School of Electrical Engineering, Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, Johor, Malaysia
2 Department of Electronic Engineering, Faculty of Electrical and Computer Engineering, NED University of
Engineering and Technology, Karachi 75270, Pakistan
3 Department of Electrical and Electronic Engineering, University of Nottingham Malaysia, Jalan Broga,
43500, Semenyih, Selangor, Malaysia
4 Department of Electrical and Computer Engineering, University of British Columbia, Vancouver, B.C.
V6T1Z4, Canada
E-mail: takahata@ece.ubc.ca and sultan_ali@fke.utm.my
Abstract
Micro-electromechanical-system (MEMS) based actuators, which transduce certain domains
of energy into mechanical movements in the microscopic scale, are increasingly contributing
to the areas of biomedical engineering and healthcare applications. They are enabling new
functionalities in biomedical devices through their unique miniaturized features. An effective
selection of a particular actuator, among a wide range of actuator types available in the
MEMS field, requires to be made through assessment of many factors involved in both the
actuator itself and a target application. This paper presents an overview of the state-of-the-art
MEMS actuators that have been developed for biomedical applications. The actuation
methods, working principle, and imperative features of these actuators are discussed along
with their specific applications. An emphasis of this review is placed on temperature-
responsive, electromagnetic, piezoelectric, and fluid-driven actuators towards various
application areas including lab-on-a-chip, drug delivery systems, cardiac devices, and
surgical tools. It also highlights the key issues of MEMS actuators in light of biomedical
applications.
Keywords: MEMS, actuators, biomedical devices, lab-on-a-chip, smart implants, surgical
devices

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1. Introduction
The rapid development of micro-electromechanical-system (MEMS) technologies has
increasingly provided means to miniaturize and advance various biomedical devices and
bioMEMS [1-4]. The applications of these MEMS-based devices include cardiac devices [5,
6], microneedles [7, 8], lab-on-a-chip devices for fast chemical/biological analysis [9-11],
microsurgical robots [12-16], and in-vivo drug delivery systems for drug release with
precision dosage and timing control [17-20]. MEMS actuators are widely used to realize
these types of devices and enable accurate control of them [21]. Serving as core architectural
elements, MEMS actuators have emerged as a promising technology that plays a vital role in
enabling a wide range of biomedical devices. Among existing MEMS actuators, those with
thermoresponsive [22], electromagnetic [23], piezoelectric [24], thermopneumatic [25], and
pneumatic [26] mechanisms have been some of the representative types widely used for
biomedical applications. Each of these actuator types possesses attractive features. For
instance, shape memory alloys (SMAs), a type of smart materials that respond to temperature,
offer high work density, large actuation force and displacement, simple structural design,
resistance to corrosion, and biocompatibility [27-29]. Electromagnetic actuators generally
provide large displacement, fast dynamic response, and an ability of low-voltage and remote
actuation [30-32]. Piezoelectric actuators are often used in ultra-precision and high-speed
applications due to their ability of nano-scale actuation, quick response, and self-locking at
power-off state [33-36]. Pneumatic microactuators are well-known for simple structure, high
flexibility, high force per unit volume, high energy density, and low cost [37-41].
The capabilities of MEMS actuators are continuously growing with a great promise for
diverse future applications. As those actuators exhibit different characteristics and
shortcomings, however, a particular type should be wisely selected and applied for a targeted
biomedical device while assessing the requirements involved in the device and its
environment. In this paper, the working principles, designs, characteristics, and their key
applications of MEMS actuators are comprehensively discussed with an aim to aid further
development of bioMEMS and other biomedical microdevices functionalized by the
actuators. This review is structured as follows: The working principles of thermoresponsive,
electromagnetic, piezoelectric, and fluid-driven microactuators are discussed in Section 2.
Section 3 presents critical applications of these actuators, including lab-on-a-chip, drug
delivery systems, cardiac devices, and surgical and endoscopic tools. The review is

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concluded with a discussion of major factors toward enabling elevated performance of these
actuators in Section 4.
2. Types of Biomedical MEMS Actuators
2.1. Thermoresponsive Actuators
SMAs, shape memory polymers (SMPs), and certain types of hydrogels are classified as
smart materials that have an ability of shape recovery when triggered by an environmental
stimulus. They commonly respond to heat, whereas specific responsive hydrogels also trigger
with others such as radiation, moisture, pH level, and magnetic and electric fields [42-47].
This section reviews these thermoresponsive smart materials regarding their phase transition
modes and characteristics that allow them to work as actuators in the micro domain.
2.1.1 SMA
The actuation of SMAs is based on the principle of a shape-memory effect called martensitic-
austenitic transformation. When a SMA is in its martensite phase, the alloy is in the form of
monoclinic crystals, which makes it more flexible and hence more easily deformed.
Following the deformation of the material’s crystalline orientation, cubic crystals are
constructed within the molecular arrangement, while the material becomes rigid and hard to
deform above the austenite temperature upon heating. When a SMA is cooled in the absence
of a load, the materials crystal structure follows twinned martensite. During this phase, the
SMA can be deformed by applying an external force or by employing a bias spring to achieve
reversible motion. The changes in the crystalline state of SMA are illustrated in Figure 1a
[48]. There are several phase transformation temperatures that must be considered when
selecting a SMA with respect to its applications. During the shape recovery process, the
transformation from the martensite cold state to the austenite hot state begins at the austenite
starting temperature and ends at the austenite finishing temperature. Meanwhile, the
transformation from the hot austenite phase to the cold martensite phase begins at the
martensite starting temperature and ends at the martensite finishing temperature. The SMA
typically consists of a few elements, and the composition level among these elements
determines the transformation temperature. In other words, the elemental composition can be
adjusted to achieve a specific transformation temperature depending on the application.
SMA actuators in the MEMS area are typically fabricated in a form of patterned thin
film or bulk-micromachined structures [49-59]. They possess general attractive attributes

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including large displacement, large force, high mechanical robustness, and corrosion-resistant
[60-66]. The NiTi alloy known as Nitinol is one of the most widely used SMA materials for
biomedical applications owing to its high biocompatibility that facilitates the application for
implantable devices such as surgical tools, cardiac devices, and drug delivery systems [22,
56, 67-71]. General disadvantages of SMA actuators lie in relatively slow temporal response
as well as high power consumption when actuated with self-heating by passing an electrical
current to the material.
2.1.2 SMP
The SMPs have gained significant interest in biomedical applications due to its general
features such as structural flexibility, large strains, low density, tunable transition
temperature, and biodegradable properties [72, 73]. These features make them suitable for
applications in endovascular and drug delivery devices [74, 75]. The thermoresponsive SMP
exhibits a shape-memory effect based on the polymer’s dual-segment system comprised of
cross-links and switching segments. The cross-links determine the permanent shape of the
polymer whereas the switching segments coupled with transition temperature fix the
temporary shape. The SMP is stiff when its temperature is below the transition temperature,
whereas heating it over the transition temperature makes it relatively soft. For shape setting,
an external force must be applied to an SMP while it is heated above the transition
temperature. This step causes the switching segments to fix the molecular chain positions.
Afterwards, the SMP is cooled while removing the external force to result in a memorized
Figure 1. Phase transformations of shape-memory materials. (a) Changes in the crystalline
orientation of SMA at different phases. Reproduced with permission [48]. Copyright 2016,
Elsevier. (b) Shape recovery process in SMP. Reproduced with permission [76]. Copyright
2016, Wiley-VCH.

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shape for the polymer. Applying heat to the SMP induces recovery of the memorized shape
through the shape memory effect as illustrated in Figure 1b [76]. Although this actuator
possesses the aforementioned beneficial properties, SMPs often suffer from slow response
and low recovery stress.
2.1.3 Temperature-Sensitive Hydrogels
Hydrogels are three-dimensional polymeric networks with hydrophilic structures that allow
the absorption of a large amount of aqueous solution in the networks [77]. Depending on the
type of cross-linking between polymers, some of them display mass reversible changes in
response to physical or chemical stimulus [77]. Poly(N-isopropyl acrylamide), or PNIPAM in
short, is a thermoresponsive hydrogel that changes its size at a phase transition temperature
called the lower critical solution temperature (LCST) in the solution [78]. When temperature
of PNIPAM hydrogel is raised above the LCST, the material shrinks by releasing the uptake
solution, whereas reducing the temperature reverses the process [79]. Different material
compositions of PNIPAM can be used to modify its LCST level to tailor it to a specific
application [80]. Besides intrinsic phase transition behavior, the hydrogels also possess
distinct attributes such as tunable mechanical and degradation features, sensitivity towards
stimuli, and ability to conjugate with hydrophilic and hydrophobic therapeutic compounds.
Additionally, PNINAM can be synthesized to be ultraviolet-light sensitive in its
polymerization, which enables precise patterning and complex structure formation of the
polymer through a photolithographic process [81]. These features have promoted the
application of PNIPAM for biomedical devices, such as microvalves in drug delivery systems
as well as encapsulation and delivery of cells [79, 82-90]. In spite of many advantages,
thermoresponsive hydrogels inherently suffer from relatively slow temporal responses similar
to SMA and SMP, and may pose leakage of the solution through the material.
2.2 Electromagnetic Actuators
Electromagnetic actuators generally employ the interaction of one or more magnetic
structures with the magnetic field (B) produced by a current-carrying circuit [91]. A common
configuration of these actuators consists of a coil and a ferromagnetic movable structure
placed in the field produced by the coil as illustrated in Figure 2 with a suspended cantilever
beam being the movable magnetic structure [92, 93]. When the driving current, i, is passed
through the coil, it produces B defined by Biot-Savart law [94, 95] as:

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(1)
where μ0, μr, Ni, and l are the permeability of free space, the relative permeability of the
material, the number of the coil’s turns, and the length of the coil, respectively. The
interaction with B induces an attractive force, F, acting on the cantilever beam to cause a
displacement, X, at the beam’s free end, which can be expressed as [96]:
(2)
where L, E, w, and t are the length of the beam, the Young’s modulus of the material, the
width of the beam, and the thickness of the beam, respectively. This type of actuators has
been used in various MEMS applications given its advantages such as simple drive mode,
high field energy density, fast response time, and large deflection that are attainable with low
input voltages [31, 32]. Their applications extend to micro positioning systems [97],
micromirrors [98, 99], microgrippers [100], and microfluidics [23, 101] for micropumps
[102, 103] and microvalves [104]. Electromagnetic actuators also exhibit common
disadvantages, e.g., volumetric scaling of produced electromagnetic forces that rapidly drop
Figure 2. Schematic diagram on the working mechanism of an electromagnetic actuator
under (a) the off state without current and (b) the on state with a driving current fed to the
solenoidal coil
creating a magnetic field to displace the ferromagnetic movable
microstructure.

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as the device size shrinks, high power dissipation for driving coils, and parasitic loss at high
frequency [105], which should be taken into account in the design of application device.
2.3 Piezoelectric Actuators
Piezoelectric actuators have been widely adopted in the fields of ultra-precision engineering
and microactuation owing to its advantageous features such as fast response, high
displacement resolution, high efficiency, compact structure, and immunity to magnetic field
[34, 106-108]. The operation of the actuators relies on the converse piezoelectric effect of a
piezoelectric crystal to induce strain by applying an electric potential to the crystalline
material [109]. The converse piezoelectric effect can be theoretically described with the
following relationships [110]:
(3)
(4)
where S, E, sE, T, D, d, and ε are the strain, the electric field, the compliance with zero field,
the surface stress, the charge displacement, the piezoelectric strain coefficient, and the
dielectric constant of a piezoelectric material, respectively. The performance of this type of
actuators largely depends on the crystal structure of a piezoelectric material where d acts as a
medium for the transduction mechanism. Given the orientations of polarization and electric
field (P and E, respectively), three different modes, i.e., longitudinal mode (d33), transversal
mode (d31), and shear mode (d15) define the actuation of the material. Figure 3a shows the
piezoelectric actuation mode with the six orientations of the coordinate systems (x, y, z, θx,
θy, and θz) and the polarization of a single layer piezoelectric crystal under P. For d33 and d31
modes, E applied parallel to P results in a longitudinal deformation (δh) and a transversal
deformation (δl) simultaneously (Figure 3b), whereas E is perpendicular to P for d15 and
produces shear deformation (δs) (Figure 3c) [111]. Among these modes, d33 and d31 provide
higher strains than d15. Piezoelectric actuators produce small strains in an accurate and fast
manner, and thus have been used for a variety of high-precision actuation applications such
as micro/nano-positioning systems [112, 113], micropumps [114, 115], and micro-robotics
[116]. In spite of their advantages, incorporation of piezoelectric materials such as lead
zirconate titanate (PZT) and lead magnesium niobate-PZT ceramics in MEMS fabrication is
often challenging due to the need for high-temperature thermal processes and the instability
of deposited materials [117, 118]. Besides, the need for relatively high driving voltages and

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the large hysteresis/nonlinearity are other factors that can limit their application range [105,
119, 120].
2.4 Fluid-Driven Actuators
Soft and flexible actuators have been attracting attention for biomedical applications as tissue
interaction with mechanically rigid actuators could lead to damage to the tissue. In this
context, many studies have looked at hyperelastic-material-based pneumatic and hydraulic
actuators. These types of actuators are typically comprised of fibreless or fibre-reinforced
polymeric channel structures that allow for supply of gas or liquid (typically air or water,
respectively) to the channels [121] (e.g., McKibben artificial muscle [122]). Once fluidic
pressure is applied to the actuator’s channel, it causes elastic deformation in its overall
structure, resulting in a designed mode of actuation such as expansion, contraction, bending
or twisting motions [123, 124]. For example, pneumatic actuators having symmetric cross
sections expand or contract, while those with asymmetric cross sections (created by, e.g.,
bonding two flexible layers with different wall thicknesses or stiffness levels), such as
Figure 3. Piezoelectric actuation modes:
(a) Orientations of the actuation field and
polarization field; (b) longitudinal and transversal modes; (c) shear mode.

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pneumatic balloon actuators (PBA), show bending deformations [125]. Likewise, two arrays
of PBAs combined in the opposite bending directions cause twisting motions (Figure 4) [126,
127]. In addition, the pneumatic actuator with a single or dual-channel structure can produce
bidirectional curling or bending motions, respectively [128-131], while a three-channelled
pneumatic soft actuator offers bending motions in up to six different directions [132]. Based
on these features, Suzumori et al. developed a flexible microactuator having three chambers
for pneumatic supply [133, 134]. The actuator had a cylindrical fibre-reinforced rubber
structure that provided 3-degree-of-freedom motions. Another study investigated a MEMS-
based hydraulic actuator based on a finger-shaped chamber structure for its actuation, which
used an integrated heater to pressurize the fluid through its thermal expansion [135]. The
fluid-driven actuators offer advantageous features such as high flexibility, large displacement,
biocompatibility (when fabricated/coated with biocompatible materials), lightweight, high
power-to-weight ratio, simple/low-cost fabrication [136, 137], which makes them suitable for
Figure 4. Overview of flexible pneumatic actuators showing four different actuation
modes. Reproduced with permission. [127] Copyright 2014, Elsevier.

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applications in medical and surgical devices, whereas the need for means of fluid supply and
pressurization, actuation precision, and miniaturization are general areas of limitations.
3. Biomedical Applications of MEMS Actuators
This section emphasizes the applications of the aforementioned actuators in biomedical areas
with a focus on lab-on-a-chip, drug delivery systems, cardiac devices, and surgical tools. The
key functions of reported devices and the particular contributions of microactuators to them
are discussed.
3.1. Lab-on-a-Chip (LoC)
LoC is a class of miniaturized microfluidic devices configured in a single-chip form that is
primarily designed for biological or chemical processing and analysis [138]. These devices
allow miniaturization and amalgamation of complex processes to be implemented on a small
chip, which otherwise needs to be operated via repetitive laboratory tasks. The key features of
these devices include compactness/portability, dramatic reduction of required chemicals and
samples, higher process controllability, and faster analysis. The parallelization of many
functions integrated on LoC is leading to an emerging trend in point-of-care diagnostics
[139]. LoC devices are functionalized by forced fluid flow through microfluidic channels
patterned on them. To control flow sequence, duration and timing, direction, and flow rate of
each fluid being processed, micro-scale pumps, and valves are integrated with the channels
on the chip, allowing for precise on-chip manipulation of small quantities of particular fluids.
Piezoelectric actuators have been one type of the actuators widely used as micropump
elements in LoC to control the fluid flow with high accuracy. For example, a multi-chamber
piezoelectric pump was reported to control the fluid flow rate [140] (Figure 5a). As a
sinusoidal signal was applied to the actuator, the chamber expanded and opened the valve,
causing the fluid flow based on the inverse piezoelectric actuation. For point-of-care testing
and chemical analysis, a plug-and-play microfluidic chip integrated a piezoelectric peristaltic
micropump was demonstrated [141]. The fluid in the microchannel was transported through
impacting actions provided by the piezoelectric actuator (Figure 5b). In order to enhance the
functionality and performance of LoCs, researchers have also incorporated surface acoustic
wave (SAW) driven piezoelectric actuators into the LoCs to precisely control fluid flows and
microparticles. SAW based actuators are advantageous in LoCs owing to their features such
as low cost, simple fabrication, fast actuation, high adaptability, contact-free particle

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manipulation, and biocompatibility [142]. For instance, Ding et al. demonstrated standing
SAW based acoustic tweezers to trap and manipulate single microparticles, cells, and
organisms in a microfluidic chip. These tweezers were shown for real-time manipulation of
microparticles by utilizing a wide resonance band of interdigitated transducers [143]. For the
fluid-driven actuation approach, a LoC based on thermo-pneumatic actuation was reported to
control the flow rate inside the microfluidic channel (Figure 5c) [144]. In addition, a multi-
throughput multi-organ-on-a-chip system was developed by utilizing a pneumatic actuator
Figure 5. LoC systems and their components. (a) Schematic and prototype of a piezo-
actuated pump. Reproduced with permission [140].
Copyright 2019, Elsevier. (b)
Piezoelectric-actuator-based microfluidic pump module. Reproduced with permission
[141]. Copyright 2019, Elsevier. (c) Thermopneumatically
actuated microchamber.
Reproduced with permission [144]. Copyright 2019, Elsevier. (d) Pneumatically driven
multi-organ-on-a-plate system, showing (top) culture device, (middle) microfluidic plates,
(bottom left) culture unit and Laplace valves, and (bottom right) membrane insert and
culture chamber. Reproduced with permission [145]. Copyright 2019, RSC publishing.

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(Figure 5d) [145]. This device could handle eight different conventional cell culture
experiments (including cell seeding, medium change, live/dead staining, cell growth analysis,
and gene expression analysis of collected cells) at a time offering a potential for drug
discovery applications.
Electromagnetic actuators are another group that has been employed in micropump
and microfluidic applications exploiting their favorable features for LoC such as rapid
response, large force, and low-voltage operation. For instance, Pradeep et al. developed an
electromagnetically actuated valves to control multiple fluid flow on a programmable
microfluidics platform (Figure 6a) [146]. The device was comprised of polydimethylsiloxane
(PDMS) based microfluidic channels and membranes with an electronic board that held
solenoids. The activation of the solenoid attracted the valve to deflect the PDMS membrane,
which in turn created a path for fluid flow. Another electromagnetically actuated micropump
was reported to provide bidirectional flow [147]. This device used two pairs of power
inductor and NdFeB magnet (Figure 6b), in which the two magnets were synchronously
Figure 6. Electromagnetically actuated microfluidic devices. (a) Schematic and image of
fabricated microfluidic channel with active valves. Reproduced with permission [146].
Copyright 2018, Elsevier. (b) Schematic diagrams of (left) a dual-chamber micropump
and (right) operating principle of the actuation with positive and negative driving
voltages. Reproduced with permission [147]. Copyright 2018, Elsevier.

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actuated under either attractive or repulsive condition (by switching the polarity of voltage
applied to the inductors) to pump the fluid inside the channel in either direction. In another
example, Tahmasebipour et al. fabricated an electromagnetic uni-/bi-directional diffuser
micropump, which used the magnetic membrane based on a PDMS-Fe3O4 nanocomposite for
its electromagnetic actuation to create fluid flow through microchannels [148]. These
micropump devices could be employed in various microfluidic and LoC devices.
3.2. Implantable Drug Delivery Systems
Advances in MEMS and miniaturization technologies have enabled implantable biomedical
devices specifically designed to assist in the diagnosis and treatment of chronic or acute
diseases. Micromachined drug delivery systems are among those emerging implantable
devices. Many of these systems are comprised of micro reservoirs that store liquid-phase
drugs and microactuators that constitute a mechanism to eject the drugs out of the systems
and deliver them to the implanted sites [149]. Aside from the significant improvement in
bioavailability of drugs, the advancement of this type of systems is expected to enable
patient-tailored, pin-point treatments of targeted diseases such as cancer, diabetes, and
osteoporosis, while significantly reducing in-vivo invasiveness of the systems due to their
miniaturized forms.
MEMS drug delivery systems use microvalves to channel/regulate the drug flow into
the diseased location [150]. Thermoresponsive hydrogels have been often used to form smart
microvalves in them [84, 86, 151-156]. A study reported an implantable drug delivery device
that was fabricated to integrate PNIPAM microvalves with a wireless resonant heater and a
drug reservoir [84]. The microvalves were patterned using an in-situ photolithography
technique and were wirelessly operated by activating the resonant heater using a tuned
external radiofrequency (RF) field. This hydrogel microvalve demonstrated 38% shrinkage in
its size upon activation that allowed for release of test drug from the reservoir. Another drug
delivery system using a thermoresponsive hydrogel valve was reported to demonstrate its
repeatable drug release mechanism controlled by induction heating [152]. This device
showed the release of drug as well as its reverse flow to refill the reservoir. A more
comprehensive study on drug delivery through a MEMS device using reversible or
irreversible polymeric valves reported reproducible release control utilizing hydrogel-based
artificial muscle [153]. Eddington et al. developed a drug delivery device by employing an
array of pH-sensitive hydrogels (Figure 7a) [154]. Besides above efforts, various studies have

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reported hydrogel-based microvalves that could be applied to MEMS-based drug delivery
[155-159]. As a different approach, piezoelectric microvalves have also been studied for the
same purpose. This was demonstrated, for example, in a study that developed a wirelessly
controlled normally-closed piezoelectric microvalve activated by an inductor-capacitor (LC)
resonant circuit (Figure 7b) [160]. The activation of the LC circuit required the field
frequency to be modulated to 10 kHz resonant frequency that matched the optimal operating
frequency of the device.
Micropumps are another essential element for MEMS drug delivery systems to
transport drugs from the reservoirs to the outlets of the systems. SMA, thermopneumatic and
piezoelectric actuators have been among those often used in micropump-driven systems. An
implantable drug delivery chip reported in [70] integrated an SMA-based micropump for the
release of stored drug from the chip. The SMA was bulk-micromachined to form a resonant
circuit, which served as a self-heat source activated by RF power transfer to allow frequency-
selective actuation and pumping of drug out of the chip. Thermopneumatic micropumps
based on a similar powering method were developed for release control [161], including
multiple drug delivery and mixing with a zigzag micromixer [162]. Piezoelectric actuated
micropumps were also reported for implantable drug delivery applications [163, 164].
Besides, a polymer-based reusable implantable drug delivery system with refillable
functionality was developed [165]. This device was designed to provide control and refillable
functionalities for broad drug compatibility. Some of the implantable drug delivery systems
were reported to integrate SMP actuators [72, 166, 167]. For example, studies reported the
SMP-pumped implantable device operated by external RF magnetic fields with an actuation
range of 140µm using a 50-mW RF power and showed an average release rate of 0.172
µL/min [72, 166]. A chemotherapy drug release system was realized using hydrolytic
degradable SMPs and was evaluated in the impact of the drug release profile [167]. Apart
from the actuation mechanisms discussed above, electrochemically driven micropumps have
been shown in several reports [168-171]. These studies integrated an electrochemical bellow
actuator, transcutaneous cannula, and a dual regulation valve to form an implantable drug
delivery device [168], showing in-vivo implementation for anti-cancer drug delivery through
wireless powering [169], and demonstrated similar devices for controlled delivery of boluses
from the fabricate prototypes (Figure 7c) [170, 171].

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3.3. Cardiac Devices
Many implantable devices are targeted at providing enhanced diagnoses and/or therapeutic
treatments for specific diseases in vivo. Cardiac implants are a good example of them.
Figure 7. Drug delivery microsystems: (a) (Left) complete microfluidic device and (right)
integrated array of hydrogel actuators. Reproduced with permission [154]. Copyright
2004, IEEE. (b) (Top left) schematic and cross-sectional diagrams of the device, and
fabrication results showing (top right) top and bottom molds and (bottom) device under
off and on states. Reproduced with permission [160]. Copyright 2018, Elsevier. (c) (Left)
schematic diagram and (right) fabrication result of wirelessly powered electrochemical
bellow micropump. Reproduced with permission [171]. Copyright 2016, Elsevier.

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Atherosclerosis is a type of cardiovascular disease where arteries become hardened and
narrowed due to plaque build-up on their inner walls. In conjunction with balloon angioplasty
to treat atherosclerosis, the endovascular mechanical implants called stents are commonly
used as chronic vascular scaffolds to keep the blood vessel open. Most of commercially
available stents are metallic, made of biocompatible alloys such as medical-grade stainless
steel and Nitinol, to configure balloon-expandable or self-expanding stents. These stents with
mesh-like walls are manufactured by laser micromachining of the specific alloy tubes. The
deployment of the self-expanding stents in arteries relies on thermoresponsive actuation of
Nitinol [170]. The stent is positioned at the target location via the delivery catheter and then
(by removing the covering sheath) allowed to self-expand to its memorized diameter through
the martensite-to-austenite phase transformation upon exposure to the body temperature [172,
173]. After their implantation, expanded stents experience elastic recoil of blood vessels,
which can lead to their mechanical failures, a continuing issue for these implants. As an
approach to address this type of failure, a Nitinol-based actuator called the recoil-resilient
ring was investigated to show its ability to improve the radial stiffness of stents when
integrated with them [174]. A newer work demonstrated multiple stage expansion of SMA-
based stent via wireless RF control aiming to address recoil and restenosis issues of stents
[175]. While not as extensive as the case of SMA, the use of SMP has also been investigated
in several studies towards self-expanding stent applications. For example, one study
presented a synthesized SMP for stent application, reporting that the polymer showed 100%
strain recovery [176]. The device displayed high rubbery shear moduli in the range of 2 MPa
and the constrained stress-strain recovery cycle showed very low hysteresis. Another work
presented a biodegradable and self-expandable SMP stent showing excellent mechanical
properties as well as biocompatibility [177].
Thermal therapy commonly known as hyperthermia is a noninvasive technique that
has been used to kill cancerous cells [178]. This therapeutic approach was also reported to be
effective in suppressing the occurrence of restenosis, the most common post-stenting
complication, and following this path, stent-based endohyperthermia was investigated to
enable post-stenting thermal stimulation in a wireless manner [179]. This active “hot” stent
was designed to electrically resonate when exposed to a RF field and implement frequency-
selective heating for vascular treatment. A stent-hyperthermia system based on this principle
was demonstrated through animal tests [180, 181]. To circumvent overheating of the stent
device under excitation, a biocompatible MEMS circuit breaker chip was developed and
integrated with the hot stents (Figure 8a) [182]. This circuit breaker chip functioned as a

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17
thermoresponsive contact switch with a SMA actuator, or an absolute temperature limiter,
enabling self-regulation of stent’s resonance and thus temperature [182, 183]. Figure 8b
shows an expansion process of the integrated stent device demonstrating automatic switching
and overheat prevention when wirelessly powered [184]. The reported circuit breaker chip
was claimed to be used for temperature regulation of other types of electronic implants.
Aside from stent related applications, shape memory materials have been utilized in
other cardiac devices that exploit their actuation and deployment triggered by the body
temperature. One example is the SMP-based rings that have been used for cardiac valve
repair to reduce mitral regurgitation [185]. Closure devices have been widely used in
intervention treatment for congenital heart disease that is known as abnormal anatomy caused
by dysplasia. Several studies were reported to develop Nitinol-based closure devices (Figure
9) [186]. This type of devices is delivered into the body using its delivery system in a
compressed state and then deployed to its original shape at the target location. A well-known
occlude device was realized with two Nitinol woven discs for closure of congenital heart
defects [187].
3.4 Surgical and Endoscopic Tools
MEMS actuators offer promising opportunities in creating novel surgical devices as well. In
particular, these actuators based on shape-memory materials, piezoelectric, and pneumatic
Figure 8. RF-powered resonant “hot” stent for wireless restenosis treatment. (a) MEMS
circuit-breaker microchip for self-regulation of stent temperature.
Reproduced with
permission [182]. Copyright 2017, IEEE. (b) Deployment of the stent device with circuit-
breaker microchip. Reproduced with permission [184]. Copyright 2015, IEEE.

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18
principles and related fabrication processes are paving avenues to miniaturizing and
improving the tools for surgical, interventional, and related procedures including catheters,
manipulators, endoscopes, and imaging devices. Utilizing the features of nanometer-range
resolution and fast response, piezoelectric microactuators have been applied for delivering
and scanning high-frequency laser pulses for microsurgery purposes. For example,
Ferhanoglu et al. reported rapid removal of bulk tumors and bones using the 5-mm-diameter
fiber device comprised of an air-core photonic bandgap fiber for delivery of high energy laser
pulses, a piezoelectric tube actuator for fiber scanning, and two aspheric lenses for focusing
the laser beam [188]. To enhance the visualization of fine biopsy needles under ultrasound
imaging, the needle-like catheter that equipped a miniaturized ultrasonic actuator was
developed with a PZT layer sandwiched between two flexible electrodes using MEMS
technology [189]. Being attached to a catheter, the actuator radiated low-intensity ultrasound
for detection of a biopsy needle tip under sonography. Likewise, to perform a non-abdominal
operation or microsurgery, a micro ultrasonic scalpel was developed using PZT deposited
through a hydrothermal method [190, 191].
Pneumatic actuators shaped with soft and flexible elastomers are considered as one of
Figure 9. Nitinol-based closure devices for congenital heart disease: (a) Amplatzer ASD
Occluder; (b) Occlutech Figulla ASD Occluder. Reproduced with permission [186].
Copyright 2019, Elsevier.

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19
the most suitable candidates for surgical device applications. Many studies utilized the
anisotropic rigidity of PBA in developing bending actuators for active catheter tools. For
example, Ruzzu et al. reported a system for fixing and orientating the catheter tip consisting
of three inflatable microballoons [192]. The microballoons were mounted on the three sides
of the catheter tip and controlled by electro-thermo-pneumatic microvalves. When deflated,
these balloons exerted a force on the wall of the vessel, causing a change in the position and
orientation of the catheter tip. In addition, a telescopic motion was achieved by connecting
several PBA pairs in series in order to actuate commercial forceps [193]. Another PBA-based
device with a cylindrical microstructure was developed to solve a bubbling problem in the
intestinal tract, which caused undesirable stagnation blocking the observation of cells [194].
Supplying air to the artificial intestinal tract via microchannel, the PBA gradually
transformed from flat to circular tube that allowed perfusion of the culture media. For
endoscopic fluorescence imaging and diagnosis, a flexible end-effector was developed via
integration of a PDMS-based PBA, serving as scanning actuator, with an SU-8 optical
waveguide using MEMS fabricated techniques [195].
Besides the PBA-based approaches, various efforts have tailored pneumatic and other
fluid-driven actuators to develop different surgical tools. For example, a pneumatically
actuated micro-gripper was reported to manipulate embryos for cloning applications, (Figure
10a) [196]. The micro-gripper consisted of two main parts; the micro pneumatic chamber
with a flexible membrane and the hinged gripper arms connected to the membrane. Supplying
pressurized air to the membrane, it deflected both the arms to provide a gripping motion.
Traditional laparoscopes used for certain surgical interventions (such as total mesorectal
excision) lack a flexibility sufficient to safely maneuver and reach difficult surgical targets.
This need was approached through the development of the robotic device composed of two
pneumatically actuated identical modules, capable of omnidirectional bending and
elongation, to allow for highly dexterous and safe navigation [197, 198]. Becker et al.
developed a tissue retraction device for treatment of lesions in the gastrointestinal tract [199].
This device was comprised of three main integrated components, i.e., a rigid expandable
geometric structure, inflatable pneumatic actuators, and a vacuum gripper fabricated using the
pop-up book MEMS technique. Similarly, to improve the distal dexterity and enable tissue
retraction, the soft pop-up actuators were exploited to form a multi-articulated robotic arm
(Figure 10b) [200]. Here, the millimeter-scale hybrid soft pop-up actuators were embedded
with capacitive sensing elements to achieve proprioceptive actuation. Endoscopic devices
also often suffer from limited distal tip dexterity, and this issue has been tacked by

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20
incorporating pneumatic actuation mechanisms with them. For example, pneumatic tubular
actuators were developed and optimized for applications in flexible microactuator-based
endoscopes to facilitate colonoscopy [201, 202] as well as a bronchoscope to observe lung
airway and obstructions in the bronchus [203]. Combining a chip-on-tip CMOS camera with
an elastic inflatable microactuator, Gorissen et al. presented a flexible endoscope for
navigating through intricate topologies of the human body [204].
The endoscopic devices with active scanning functions have been developed by
adopting different actuation methods besides pneumatic one. For example, to obtain in-vivo
local images for tissue diagnostics, an active optical coherence tomography (OCT) probe was
developed with two-axis scanning electrothermal MEMS micromirror, gradient refractive
Figure 10. MEMS-enabled surgical and endoscopic tools. (a) Pneumatically actuated
micro-gripper. Reproduced with permission [196]. Copyright 2015, Elsevier. (b)
Conceptual 3D model and optical image of the soft pop-up actuator. Reproduced with
permission [200]. Copyright 2014, Elsevier. (c) Electrothermally actuated MEMS
scanning mirror for OCT probe and optical images of fabricated micromirrors.
Reproduced with permission [205]. Copyright 2008, IOP Publishing. (d) MEMS-based 3D
confocal scanning microendoscope. Reproduced with permission [207]. Copyright 2013,
Elsevier. (e) Side-viewing Raman probe with integrated MEMS rotary motor. Reproduced
with permission [208]. Copyright 2019, Wiley-VCH.

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21
index lens, and single-mode fiber integrated on silicon optical bench (SiOB) substrate (Figure
10c) [205]. For three-dimensional (3D) imaging, a 2-axis MEMS mirror with a preset (45°)
angle was directly integrated on a SiOB. The probe was enclosed within a biocompatible,
transparent and waterproof polycarbonate tube for in-vivo applications. A similar active OCT
probe enabled by an electrothermal MEMS mirror was also reported for real-time imaging of
internal organs such as gastrointestinal tract, stomach, small intestine, and esophagus [206].
The unique features of this MEMS-mirror design were a large scan range of ±30°, a high
speed of about 2.5 frames per second, and a body-safe driving voltage of 5.5 V. Following
the same scanning approach, a fiber-optic 3D microendoscope with a confocal scanning
function was developed for early cancer diagnosis (Figure 10d) [207]. The probe was
comprised of electrothermal MEMS scanning mirrors that offered a large imaging field via
both lateral and axial scans with low driving voltages. For endoscopic probes, full
circumferential scanning around the probe is an important ability for screening and detecting
lesions on the walls of luminal organs without blind spots; however, this need is difficult to
meet with 2D MEMS scanners. A tubular MEMS rotary motor was developed for this
application segment and enabled a side-viewing Raman spectroscopy (RS) probe (Figure
10e) [208-210]. This electromagnetic MEMS motor, developed using a self-sustained
ferrofluid bearing in the catheter tube, provided both stepping and continuous rotations of a
probing laser beam and demonstrated full 360° tissue imaging/analysis via RS [208] as well
as OCT [210] modalities ex vivo and in vivo. The motor was also engineered to provide
hydraulic axial motion in addition to rotation for 3D luminal imaging without requiring an
external probe positioning system [209].
4. Conclusion
Continuous advancement of microactuator technologies, along with their fabrications and
integration methods, has led to the emerging areas of biomedical microsystems including
smart implants and surgical devices in miniaturized forms. The success in a targeted
application critically relies on the appropriate selection of a particular actuator, which
depends on various factors besides the fundamental performance of the actuator itself,
including powering and control methods, biocompatibility, level of required packaging, and
cost effectiveness. With an aim to facilitate the development of this emerging field while
addressing those key factors, this paper has presented a comprehensive review of the MEMS
actuators investigated for their biomedical uses with a focus on several common transduction

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22
types. Table 1 presented a clear comparison of these actuation techniques and their
characteristics. The use of thermoresponsive materials is a promising route to enabling smart
actuation functions with simple designs, an advantageous feature towards device
miniaturization. Among them, SMA offers large displacement and force whereas SMP
possesses relatively high recoverable strain levels. The PNIPAM hydrogel can be compatible
with the standard photo-patterning process and allows for adjustment of its temperature
threshold. The above attributes often make them suitable for applications in drug delivery,
cardiac and surgical devices. The electromagnetic actuators with their large displacement,
fast response and low-voltage powering features are usable for the development of LoC and
their active elements such as micropumps and microvalves. The piezoelectric actuators are a
powerful enabling technology for devices targeted at micro/nano-scale positioning,
micropumps, and micro-robotics. Being softer and flexible, the fluid-driven actuators offer a
variety of application opportunities in surgical devices.
Exploiting these favorable features, thermoresponsive, electromagnetic, and
piezoelectric actuators are widely applied for implantable devices. However, they require an
attention in a few factors. For their medical and implant applications, these actuators are often
powered using batteries. This may cause not only the need for periodic replacement through
surgical procedure but also significantly increase the overall device sizes and hence their
invasiveness in the body. While wireless powering and control methods for smart implants
are being widely explored, the issues around their efficiency, reliability, and
biocompatibility/safety will need to be addressed. The safety factor includes proper heat
management and necessary packaging that, in turn, can negatively impact on the device
performance and size. One of the key approaches to addressing powering issues would be in-
situ energy harvesting from the implanted environment, which may be achieved using similar
principles of some of the abovementioned MEMS actuators but with reversed transductions
converting environmental stimuli to electrical energy.

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23
Types
Working
principle
Advantages
Disadvantages
Energy
density
(J/m3)
Efficiency
(%)
MEMS Applications
Thermoresponsive
actuators
SMA
Shape-
memory effect
• Large displacement
• Large force
• High mechanical
robustness
• Corrosion-resistant
• Slow temporal
response
• High power
consumption
~107
[211]
<10
[212, 213]
Surgical tools [22, 68]
Implantable devices [65]
Microgrippers [60, 67]
Micropumps [60, 63, 70]
SMP
Shape-
memory effect
• Structural flexibility
• Large strains
• Low density
• Tunable transition
temperature
• Biodegradable
properties
• Slow temporal
response
• Low recovery
stress
2-6×105
[214]
<10 [213]
Endovascular devices [74, 75,
176, 177, 185]
Drug delivery devices [74,
166, 167]
Temperature-
Sensitive
Hydrogels
Phase
transition
• Tunable
degradation features
• Tunable mechanical
features
• UV-sensitive
• Slow temporal
response
3.5×105
[211]
1.32 [215]
Surgical tools [85]
Microvalves [153-157]
Drug delivery [84, 86, 88-90,
151, 153]
Electromagnetic actuator
Magnetization
effect
• Simple drive mode
• No nonlinear effect
• High field energy
density
• Fast response
• Large deflection at
low input voltage
• High power
dissipation for
driving coils
• Volumetric scaling
of produced
electromagnetic
forces that rapidly
drop as the device
size shrinks
4×106
[213]
>90
[212, 213]
Microgrippers [100]
Micropumps [101-103]

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Table 1. Performance comparison of actuation techniques
• Parasitic loss at
high frequency
Microvalves [104]
Piezoelectric actuator
Piezoelectric
effect
• Fast response
• High displacement
resolution
• High efficiency
• Compact structure
• Immunity to
magnetic field
• Require high-
temperature thermal
processes for
incorporation of
piezo materials
• High driving
voltage
• Large hysteresis
nonlinearity
105 [213]
>90
[212, 213]
Micropumps [114, 115]
Micro-robotics [116]
Fluid-Driven actuator
Elastic
deformation
• High flexibility
• Large displacement
• Lightweight
• High power-to-
weight ratio
• Simple/low-cost
fabrication
• Low force exertion
• Limited number of
degree of freedom
1.2×106
[216]
30-40
[212, 213]
Medical and surgical devices
[136, 137]

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25
Acknowledgments
This work is partially supported by Universiti Teknologi Malaysia under UTM Shine
Program (GUP 17H61) and Prototype Development Fund (UTMPR 00L28), and Ministry of
Education Malaysia under Prototype Development Research Scheme (PRGS 4L690) and the
Fundamental Research Grant Scheme (FRGS/1/2019/TK05/UNIM/02/2).
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