Bio-Inspired Micro-Robotics for Medical Applications: A Comprehensive Review

Abstract:
Advances in microfabrication, materials science, and control systems have propelled recent
progress in bio-inspired micro-robotics—an emerging field at the crossroads of biology, robotics,
and medicine. This rapidly evolving field holds the potential to revolutionize medicine. Micro-
robots are diminutive devices, typically measuring less than a millimeter in size, capable of
remote control via magnetic fields, light, or ultrasound. Bio-inspired micro-robots are
meticulously engineered to emulate the designs and locomotion of natural organisms, such as
bacteria, sperm cells, and insects. Bio-inspired micro-robots offer several advantages over
conventional medical devices. They are less invasive, more precise, and can access anatomical
regions that are challenging or impossible to reach with traditional tools. Moreover, they can
undertake exceedingly delicate or intricate tasks, surpassing human hands' capabilities. However,
these robots must navigate the intricate and viscous environments within the body. Researchers
have developed micro-robots capable of swimming through blood vessels and maneuvering
around cells. These robots have the potential to diagnose diseases, administer drug treatments, or
perform surgical procedures. This comprehensive review delves into recent advancements and
the applications of bio-inspired micro-robots in the realm of medicine.

Keywords: Micro-robotics; Medicine; Locomotion; Drug Delivery; Minimally Invasive Surgery;

Diagnostic and Imaging.

1. Introduction:

 Introduction to bio-inspired micro-robotics and its significance in the medical field.

 A brief overview of the challenges and limitations of traditional medical procedures.
 Explanation of how bio-inspired micro-robots can address these challenges and improve
medical diagnostics, treatment, and surgery.

2. Bio-Inspired Locomotion:
Nature has provided many locomotion strategies for different environments by drawing
inspiration from organisms like fish, birds, insects, and microorganisms. We require versatile
propulsive strategies that reconcile the physical constraints of airborne and aquatic environments
to develop robots capable of hybrid aerial and aquatic locomotion [1]. Among microrobots, one
class of organisms that inspired locomotion was bacteria. Bacteria were found to exploit
mechanics to display remarkable plasticity in response to locally changing physical and chemical
conditions [2]. Breakthroughs in particle synthesis have facilitated the development of colloid
aggregates based on active matter to convert ambient or stored energy into self-propulsion [3][4].
Other examples of organisms inspiring the locomotion of robots were Basilisk lizards [5], water
snails [6], Mesovelia [7], and water striders [8], who were observed to move freely on the
surface of the water. With an average velocity of 60 body lengths per second, water striders used
their central hydrophobic legs to strike the water surface in a sculling motion. During the strike,
fore-aft contact force differences between the central hydrophobic legs were generated as a
propulsive force and provided a mechanism for their movement. Inspired by common water
striders, the synthesis of an active hydrogel poly(hydroxyethyl methacrylate-co-acrylic acid)
[p(HEMA-co-AA)] that could move autonomously on the water surface for 210 min without
external energy input occurred [9].

Images

The robot was inspired by jellyfish's swimming mechanism, which uses muscle contraction and
elastic recoil to propel themselves through the water [10]. The robot comprises a modular body
of three segments, each actuated by a magnet. The magnets are arranged to be rotated to produce
different swimming motions. The robot is controlled by a microcontroller that sends signals to
the magnets to produce the desired movement. The robot was tested in a water tank and was
shown to be able to swim in a variety of directions and at different speeds. The robot was also
able to navigate through obstacles and avoid collisions. The results of this study demonstrate the
feasibility of using bio-inspired magnetic actuation for microrobots. The robot's modular design
makes it easy to assemble and disassemble, and its magnetic actuation system provides precise
control over its movement. This makes it well-suited for various applications, such as drug
delivery, minimally invasive surgery, and environmental monitoring. The robot's swimming
ability generated thrust of up to 0.5 mN. This is a significant achievement, demonstrating that the
robot can swim against currents and other disturbances.

3. Key Technologies for Micro-medical robots

3.1 Materials for Microbots

Intro…

Fluorescent magnetic spore-based microrobots (FMSMs)

FMSMs are a type of microrobot that is made from spores that have been coated with magnetic
nanoparticles and functionalized carbon dots. FMSMs have a droplet-like morphology, good
magnetic properties, excellent red fluorescence, and selective targeting ability. They can be
magnetically propelled to perform locomotion in different media, including aqueous, saline, and
even gastrointestinal tract mucus. The motion of FMSMs can be controlled by adjusting the
magnetic field parameters. FMSMs can track C. diff toxins in different samples in real-time.
When FMSMs encounter C. diff toxins, their fluorescence is quenched. This quenching effect
can detect the presence of C. diff toxins within tens of minutes. FMSMs show great potential for
rapid and sensitive detection of C. diff toxins in clinical samples [11].

Smart materials for microrobots

Smart materials can change their properties in response to external stimuli, such as temperature,
light, or electric fields. This makes them ideal for use in microrobots because they can be used to
create robots that are more efficient, more controllable, and more adaptable. For example, smart
materials [12] can create microrobots that can move more efficiently through fluids, even thick
ones like blood. They can also be used to create safe microrobots in the human body and even
interact with the body in specific ways. For example, smart materials could create microrobots
that can release drugs only in response to a certain chemical signal. Smart materials are still
under development, but they can potentially revolutionize the field of microrobotics. In the
future, microrobots made with smart materials could be used to perform all sorts of amazing
tasks that would be impossible with current technology. Smart materials could be used to create
FMSMs that are even more efficient, controllable, and can move more efficiently through thick
fluids, such as blood or mucus. Smart materials could also be used to create FMSMs targeted
more specifically to C. diff toxins.

3.2 Fabrication and assembly techniques

Intro….

4D Printing

4D printing is a promising new technology for fabricating microrobots with complex shapes and
smart materials. Smart materials can change shape or properties due to external stimuli like
temperature, light, or magnetic fields. This allows for the creation of microrobots that can self-
assemble, morph, and adapt to their environment. 4D printed microrobots [13] can revolutionize
the field of microrobotics. For example, they could be used for drug delivery, minimally invasive
surgery, and environmental monitoring. However, some challenges need to be addressed before
4D printing can be widely used for microrobotics applications. These challenges include
developing new smart materials with improved properties, improving the accuracy and
repeatability of 4D printing, and developing new control strategies for 4D printed microrobots.
[13]

Direct Laser Written

Micromanipulation is a challenging task that requires precise control of the forces applied to
delicate objects. Direct Laser Writing (DLW) [14] can fabricate compliant micromanipulator
end-effectors to prevent object damage during manipulation. Compliant micromanipulator end-
effectors have significantly improved the dexterity and robustness of micromanipulation tasks.
They can be used in various biomedical and industrial applications, such as in vitro fertilization,
cell surgery, and the assembly of delicate electronic components. 4D printing and DLW are
promising new technologies for fabricating microrobots and micromanipulator end-effectors. 4D
printing can be used to create microrobots with complex shapes and smart materials, while DLW
can be used to fabricate compliant micromanipulator end-effectors. The combination of these
two technologies could lead to the development of next-generation microrobots with advanced
capabilities. For example, 4D-printed microrobots could be equipped with DLW-fabricated
compliant end-effectors to manipulate delicate objects rapidly[14].
Compare DLW with 4DP
3.3 Actuation of micro-medical robots
Intro…
Pneumatically actuation:
Researchers have developed a pneumatically actuated microgripper [15] with dual manipulation
and force-sensing functions. The microgripper is made of two metal arms controlled by air
pressure and can be programmed to measure the gripping force for grasping the object.
The microgripper could be used for various tasks, such as manipulating embryos for cloning or
picking and placing cell aggregates for bio-fabricating synthetic tissues. The researchers plan to
make the micro-gripper even smaller and improve its ability to sense objects.
Optically actuation:
A new method has been developed for measuring the elasticity of single cells using light-
controlled microrobots[16]. The method is non-destructive, fast, and sensitive, and it could be
used to study the elasticity of cells under different conditions and develop new therapies for
diseases caused by changes in cell elasticity. The microrobots are fabricated using two-photon
polymerization and have a probe tip that can be used to indent the cell surface. The force applied
by the microrobot and the resulting indentation are measured to calculate the cell's Young's
modulus.
The method has several advantages over existing methods for measuring cell elasticity.
First, it is non-destructive, that the cells can be imaged and studied after the experiment. Second,
it is relatively fast and can be used to measure the elasticity of multiple cells in a single
experiment. Third, it is sensitive enough to measure the elasticity of soft cells. The researchers
suggest that their method could be used to study the elasticity of cells under different conditions,
such as in response to drugs or disease. They also suggested that it could be used to deliver drugs
into cells or perform other tasks minimally invasively.
All three of these sections discuss different ways to actuate micro-medical robots.
Piezoelectric tactile sensors can be used to measure the mechanical characteristics of soft
materials, which could be useful for developing new surgical procedures. Pneumatically actuated
microgrippers can be used for various tasks, such as manipulating embryos or picking and
placing cell aggregates. Optically actuated microrobots can be used to measure the elasticity of
single cells, which could be useful for developing new therapies for diseases caused by changes
in cell elasticity.
These are just a few examples of how micro-medical robots can be actuated. As the field of
micro-robotics continues to develop, we can expect to see even more innovative and
sophisticated ways to control these tiny machines.

3.4 Sensing capability in Micro-medical robotics

This section presents a microforce-sensing mobile microrobot (µFSMM) [17] for automated
micromanipulation tasks. The µFSMM has a planar vision-based micro force sensor end-effector
and a chemically etched nickel body driven by an external magnetic field. The micro force
sensor end-effector can measure forces from 0-20 µN. The µFSMM has been demonstrated to
perform automated micromanipulation tasks with real-time, closed-loop force control. For
example, the µFSMM has been used to apply a prescribed force of 6 µN to a desired location on
a fixed micro-object. The µFSMM has also been used to limit the manipulation forces
experienced by a micro-object to remain below a threshold of 12 µN.
Overall, the µFSMM is a promising new platform for automated micromanipulation tasks. It can
measure and control forces in the micronewton (µN) range, essential for many delicate
micromanipulation tasks. The µFSMM is also relatively simple to fabricate and operate, making
it a practical solution for various applications.

AI Advances in Medical Microbots

Artificial intelligence (AI) has the potential to revolutionize the field of medical micro-robotics.
AI-powered microrobots could be used to perform a wide range of tasks, such as:
 Targeted drug delivery: AI could be used to develop microrobots that can navigate
through the bloodstream and deliver drugs directly to a tumor site. This could help
improve cancer treatments' efficacy and reduce side effects.
 Minimally invasive surgery: AI could be used to develop microrobots that can perform
surgery through small incisions. This could reduce the risk of complications and speed up
recovery time.
  Cell manipulation: AI could be used to develop microrobots that can precisely
manipulate cells. This could be used for various applications, such as tissue engineering
and regenerative medicine.
AI is still in its early stages of development, but it has the potential to transform the field of
medical microrobotics. By combining AI with micro-robotics, researchers are developing new
tools that could revolutionize how diagnosis and treatment for diseases is carriedout.
3.5 Intelligence for Micro-medical Robots
Intelligence is an essential component of micro-medical robots. Intelligent micro-robots can
perceive their environment, make decisions, and adapt to changing conditions. This allows them
to perform complex tasks that would be impossible for traditional robots.
Physical Intelligence
Physical intelligence is the ability of a robot to interact with its environment in a meaningful
way. This requires the robot to have a variety of sensors, actuators, and control systems.
Shape-Memory-Alloy (SMA)
One example of a micro-robot with physical intelligence is the SMA micromanipulator [18].
This micromanipulator uses SMA actuators to control the displacement of a gripper. The gripper
is compliant, which allows for force feedback and two-way actuation. The micromanipulator is
fabricated using a simple method that can be scaled to manipulate a single biological cell.
The SMA micromanipulator has the potential to be used in a variety of applications, such as
microassembly, microsurgery, and cell manipulation. The compliant gripper design makes it
possible to control the gripping force with high precision, which is essential for many
applications.
Carbon Nitride-Based Light-Driven Microswimmers
Another example of a micro-robot with physical intelligence is the carbon nitride-based light-
driven microswimmer [19]. These microswimmers are propelled by the self-diffusiophoresis of
charged species generated on their surface by light-induced redox reactions. The microswimmers
can also be photocharged in hydrogen peroxide (H2O2), allowing them to swim even in the dark
for extended periods. These microswimmers can be applied in targeted drug delivery,
environmental remediation, and other areas.
Artificial Intelligence
Artificial intelligence (AI) is another important component of micro-medical robots. AI can
control the robots, make decisions, and learn from experience.
Reinforcement Learning with Artificial Microswimmers
One example of how AI controls micro-medical robots is in developing reinforcement learning
(RL) algorithms. RL algorithms allow robots to learn how to behave in an environment by trial
and error. Researchers have demonstrated how RL can control artificial microswimmers [20].
They showed that the microswimmers could learn to navigate a grid world successfully, even in
the presence of noise. They also showed that the microswimmers can learn to cooperate with
other microswimmers to reach a common goal.
Deep Reinforcement Learning
Another example of how AI is being used to control micro-medical robots is in the development
of deep reinforcement learning (DRL) algorithms. DRL algorithms are RL algorithms that use
deep neural networks to learn complex policies. Researchers have developed a DRL algorithm
that can be used to control micro/nanomotors with different translational and rotational dynamics
to perform localization and navigation tasks [21]. The DRL algorithm was trained on extensive
navigation data in different scenarios to learn robust navigation strategies. The researchers found
that full-control and rotor motors can reach the target faster than translator motors.
This study provides a comprehensive understanding of DRL-controlled micro/nano motor
navigation and localization. The findings could guide the design of future autonomous
micro/nanomotor systems that can operate in complex and diverse environments. Intelligence is
an essential component of micro-medical robots. Intelligent micro-robots can perform complex
tasks that would be impossible for traditional robots. Physical and artificial intelligence are being
used to develop intelligent micro-medical robots. Physical intelligence allows robots to interact
with their environment meaningfully, while artificial intelligence allows robots to control
themselves, make decisions, and learn from experience. The development of intelligent micro-
medical robots has the potential to revolutionize the way we diagnose and treat diseases.

4. Applications of Microrobots in the Medical industry

4.1 Drug Delivery
Microrobots for active drug delivery are a promising new technology with the potential to
revolutionize the way we treat diseases. An important criterion for developing microrobots with
an application in drug delivery is that they should be biocompatible and durable enough to
withstand the environment of the body it enters into. Another criterion to keep in mind is that the
microrobots must be accurately programmed to navigate to specific target sites. Considering
these, the research on microrobots for active drug delivery is progressing rapidly. There are
clinical trials taking in place to test the safety and efficacy of microrobots for treating cancer,
cardiovascular disease, and other conditions.
If successful, microrobots could provide patients with new and minimally invasive options for
treatment. Microrobots could also be used to deliver drugs to areas of the body that are difficult
to reach with traditional methods [22]. For instance, researchers evolved untethered miniature
robots, or microrobots, with the potential to revolutionize minimally invasive analysis and
treatment of illnesses inside the digestive system. Microrobots have been propelled by way of
outside fields or self-powered through chemical reactions, and they have been ready with sensors
and actuators to perform complicated responsibilities such as drug delivery.

Microrobots supplied several advantages over traditional methods for centered transport and
remedy inside the digestive system. First, they were much smaller and more maneuverable than
conventional gadgets, allowing them to access slender and tortuous passages. Second,
microrobots might be programmed to navigate to precise areas of the digestive tract, handing
drugs or different healing dealers immediately to the affected location. Third, microrobots could
be used with sensors to display the local environment and modify their behavior.

Several exclusive varieties of microrobots were developed for use in the digestive device.
External magnetic fields propelled magnetic microrobots were used to deliver capsules or
perform minimally invasive surgical operations. Microrobots powered through chemical
reactions should swim via the digestive tract using flagella or different propulsion mechanisms.
Biohybrid microrobots blend synthetic and biological additives with pink blood cells or
microorganisms to create robots better suited to the human body.

4.2 Minimally Invasive Surgery

Microrobots could be used to deal with numerous diseases within the digestive device, including
cancer, inflammatory bowel sickness, and inoperable strictures. For instance, microrobots will
deliver chemotherapy capsules directly to tumors or supply stem cells to damaged tissues.
Microrobots can also remove polyps or other growths from the digestive tract. The development
of microrobots for centered transport and remedy in the digestive gadget changed in its early
stages, but there has been vast development in recent years. Several scientific trials were
underway to check the safety and efficacy of microrobots for treating precise illnesses [23].

Researchers developed several methods for bioinspired microrobots for targeted cancer therapy.
One common method was microfabrication, which involved using techniques such as
lithography and etching to create microrobots from materials such as silicon, glass, or polymers.
Another common method was self-assembly, which involved using biological or synthetic
molecules to assemble microrobots from smaller components. Bio-hybridization, which involved
combining synthetic and biological components to create more compatible microrobots with the
human body, was also a common method. Once microrobots had been created, they could be
controlled using different mechanisms. External fields, such as magnetic, electric, or ultrasound
waves, could be used to manipulate the microrobots' movement. Chemical reactions and
biological molecules, such as enzymes or antibodies, could also activate the microrobots' sensors
and actuators and propel them to a specific target site [24].

A new type of magnetically actuated microrobot for drug delivery and magnetic nanoparticle
retrieval, it is of a helical structure covered with magnetic nanoparticles and a drug payload. The
helical structure consists of a sequence of interconnected earrings, which gave the microrobot a
corkscrew-like form. The magnetic nanoparticles were attached to the helical shape's surface
using a biocompatible polymer. The drug payload became encapsulated inside the helical
structure using a biodegradable polymer. The microrobot becomes controlled using a magnetic
subject. The magnetic area turned into applied the usage of outside magnets or electromagnets.
The magnetic area might govern the microrobot's motion and navigate it to a target website.
Once the microrobot reaches the goal site, it can supply the drug payload by liberating it through
the partitions of the helical structure. The microrobot may then be retrieved by applying an
opposite magnetic field to draw the magnetic nanoparticles back to the surface of the microrobot.
The microrobot is biocompatible and may be utilized in vivo. It could be tested in vitro and in
vivo, and it's shown to be powerful for handing over drugs to cancer cells and retrieving
magnetic nanoparticles from tissues [25].

Shape-switching microrobots were a new type of microrobot that could change their shape in
response to external stimuli. This ability to change shape gave shape-switching microrobots
several advantages over traditional microrobots, including enhanced drug delivery and
locomotion. These microrobots are made from polymers, metals, and hydrogels. They were
triggered to change shape using different types of stimuli, including temperature, light, and
magnetic fields. These microrobots were used to deliver drugs to specific target sites. One type
of shape-switching microrobot developed for medical applications is made of a polymer that
changes shape in response to temperature. This type of microrobot can deliver drugs to specified
target sites in the body by changing their shape to navigate through the bloodstream and into the
target tissue.
Another type of shape-switching microrobot developed for medical applications is made of a
metal that changes shape in response to magnetic fields. This type of microrobot can be used to
deliver drugs to specific target sites in the body by being guided to the target site using a
magnetic field. Shape-switching microrobots can also be used to perform minimally invasive
surgery. For example, a shape-switching microrobot could remove a blockage from a blood
vessel or repair damaged tissue [26].

4.3 Diagnostic and Imaging:

Medical imaging of microrobots is a rapidly developing field with the potential to enable real-
time tracking and control of microrobots in vivo. This is essential for the safe and effective
delivery of microrobots to target tissues and organs and for monitoring their therapeutic effects.
Various medical imaging modalities can be used to image microrobots, including optical
imaging, magnetic resonance imaging (MRI), ultrasound imaging, and computed tomography
(CT). Optical imaging is a versatile modality that can image microrobots in vivo with high
spatial resolution. However, optical imaging is limited by its depth penetration and susceptibility
to scattering from tissues. MRI is another powerful imaging modality that can image microrobots
in vivo with high soft tissue contrast and penetration depth. However, MRI can be challenging
for imaging microrobots due to their small size and susceptibility to magnetic fields. Ultrasound
imaging is a real-time, noninvasive modality that can image microrobots in vivo with good
spatial resolution. However, ultrasound imaging is limited by its penetration depth and
susceptibility to interference from surrounding tissues. CT is a high-resolution imaging modality
that can image microrobots in vivo with good penetration depth. However, CT is limited by its
exposure to ionizing radiation [27].
Another approach was using a powerful magnetic stem cell-based microrobot for low-density
stem cell delivery via the nasal route in a mouse brain. The microrobot was fabricated by
embedding stem cells in a hydrogel matrix, and the hydrogel was then coated with magnetic
nanoparticles. The microrobot could transmit a magnetic field through the nose to the brain. In-
vivo experiments have shown that microrobots can efficiently deliver stem cells into the brain
and minimize damage to the surrounding tissue. The microrobot was designed to be
biocompatible and biodegradable. The hydrogel matrix is made from a material commonly used
in implants, and the magnetic nanoparticles are made from a non-toxic material and easily
removed from the body. This makes the microrobot a promising candidate for will be interpreted
clinically. Microrobots can deliver stem cells to the brain, such as treatments for stroke,
Parkinson's disease, and Alzheimer's. The oral route is less invasive and can deliver stem cells to
the brain without surgery. Overall, the magnetically actuated stem cell-based microrobot
developed in this study is a promising alternative for low-cost stem cell delivery. The microrobot
is biocompatible, biodegradable, and can be magnetically transferred through the nose to the
brain. This additionally makes it an option for clinical translation for treatments [28].

Coming to the application of microrobots in diagnostics and imaging, medical microrobots have
the potential to revolutionize surgery, therapy, imaging, and diagnostics. Microrobots could be
used to image internal organs and tissues at high resolution, improving the diagnosis and
monitoring of diseases. For example, microrobots could be used to image the inside of blood
vessels to detect plaque buildup or the inside of the brain to detect tumors or other abnormalities.
Microrobots could collect samples from inside the body for diagnostic purposes. For example,
microrobots could be used to collect a biopsy sample from a tumor or a sample of cerebrospinal
fluid from the brain. But this comes with its technical challenges, too. They must be addressed
before medical microrobots can be widely used in clinical practice. These challenges include:
 Developing biocompatible and safe microrobots.
 Developing methods to control and navigate microrobots in vivo.
 Developing imaging methods to track and monitor microrobots in vivo.
 Integrating microrobots with existing medical devices and procedures.
Despite these challenges, significant progress is being made in medical microrobots. Researchers
are developing new materials and fabrication techniques to create biocompatible and safe
microrobots. They are also developing new methods to control and navigate microrobots in vivo
and to image and track them in real-time. As the field continues to develop, one can expect to see
medical microrobots playing an increasingly important role in diagnosing and treating diseases
[29].
There is one such imaging technique, namely, ultrasound imaging. It can track micro/nanorobots
in vivo using various techniques, including B-mode ultrasound imaging, which uses reflected
sound waves to create images of objects. Microrobots can be distinguished from surrounding
tissues based on their acoustic properties, such as size, shape, and material composition. Doppler
ultrasound imaging can be used to measure the velocity of moving objects. This can be used to
track the movement of microrobots through the body. Speckle tracking imaging can be used to
track the displacement of objects over time. This can be used to track the movement of
microrobots even when they are not moving in a straight line.
Contrast-enhanced ultrasound imaging can improve the visibility of microrobots in ultrasound
images. This can be achieved by injecting microbubbles into the bloodstream, which scatter
ultrasound waves. Photoacoustic imaging is a hybrid imaging modality that combines ultrasound
imaging with optical imaging. It can be used to track microrobots that are photo-acoustically
active, such as microrobots that contain gold nanoparticles. These techniques can track
micro/nanorobots in vivo in real-time. This information can guide the movement of microrobots
to specific target sites in the body. Ultrasound imaging-guided micro/nanorobotics has the
potential for various biomedical applications, such as drug delivery, targeted therapy, and
minimally invasive surgery.
However, some challenges still need to be addressed before ultrasound imaging can be widely
used for micro/nanorobotics applications. One challenge is that ultrasound imaging can be
sensitive to noise and artifacts. Another challenge is that the tracking accuracy of
micro/nanorobots can be affected by factors such as the size and density of the swarm [30].

4.4 Cell characterization and pathogen sensing

A wireless self-sensing microrobot that uses artificial intelligence is based on a local magnetic
field enhancement in electromagnetic imaging for noninvasive monitoring in vivo. The
microrobot is based on local magnetic field enhancement and electromagnetic imaging for
noninvasive monitoring in vivo. It consists of a head equipped with a sensor working as a radio
frequency (RF) coil that is tunable and a magnetic tail that an external magnetic field can drive.
A sensor circuit is made up of a thin-film-electrode inductor-capacitor circuit connected by
through holes. The RF coil's size and number of interdigital electrode pairs can vary according to
the requirements. The microrobot can monitor various physiological parameters such as pH and
temperature. The variable pH and temperature of the solutions can affect the influence of the
resistance and resonance of the frequency circuit. Interestingly, the microrobot can be used to
detect lesions in the body. When it reaches the vicinity of the lesion, the enhanced signal can be
changed, indicative of the occurrence of possible disease[32].

The medical capsule robots use chemical interaction because of certain environmental conditions
to release the drugs out of the capsule or use non-mechanical energy to release the drug. These
systems are bifurcated into active and passive drug delivery systems. A response is triggered in
the passive non-mechanical systems when a chemical interaction occurs in the capsule due to
certain nearby criteria. An example is releasing drugs into the colon [33]. However, these
systems do not offer any control over drug release, the precise targeted drug delivery is not
achieved, and the release rate can't be tuned. In active non-mechanical systems, non-mechanical
energy pumps the drug out of the capsule. The energy required can be generated using
magnetohydrodynamic, electro-hydrodynamic, electro-osmotic, electro-wetting, and
electrochemical energy. In a prototype, magnetohydrodynamic energy is used to empty the drug
reservoir. It has the advantage of accommodating more space for the drug reservoir [34]. In an
attempt to perform in vivo surgery with a capsule robot, a novel endoscopic capsule has been
proposed by Valdasri et al. [35]. The capsule's dimensions are 12.8mm x 33.5 mm. It constitutes
four magnets that activate the locomotion by interacting with the external magnet. A nitinol clip
is placed on top of the capsule to be released upon receiving a signal. The capsule could clip the
iatrogenic bleeding, thus proving the capability of a capsule robot to perform multi-functional
tasks like diagnosis and treatment [36].

4.5 Biopsy and Pathogens Collection

Micro-robot integration has ushered in a new era for medical diagnostics and microbiology.
Tissue biopsy, the cornerstone of noninvasive disease diagnosis, has been significantly enhanced
by untethered endoscopic micro-grippers, enabling precise and efficient tissue sample retrieval.
These micro-robots have proven their efficacy in both in vitro and in vivo biopsy procedures,
offering mass-producibility and remote actuation capabilities [37].

Recent developments have introduced untethered micro-robots for in vivo biopsy, exemplified
by magnetically actuated soft capsule endoscopes and stimuli-responsive soft grippers for
targeted drug delivery [37]. Furthermore, micro-robots have expanded their utility to pathogen
collection, with innovative designs mimicking an onion's multilayer structure, attracting and
capturing motile microorganisms [37]. While micro-robots hold immense promise, challenges
like specimen preservation and contamination prevention remain areas of active exploration.
Nevertheless, the marriage of micro-robotics and healthcare stands to revolutionize diagnosis and
disease management, offering creative solutions to longstanding medical dilemmas.

Microbots revolutionize biopsy and pathogen collection, boasting precision with up to 95%
accuracy and minimal invasiveness, translating to shorter recovery times [38]. They enhance
sample quality for pathogen collection, facilitate real-time monitoring for informed decision-
making, and maintain rigorous safety standards. Long-term data reveal improved patient
outcomes, while cost-effectiveness analyses are ongoing [38]. In a study comparing frameless
and frame-based brain biopsies on 56 patients, both techniques yielded similar diagnostic results
(10.7% vs. 14.3%) [3]. Frameless biopsies were quicker (79.1 vs. 111.3 minutes) with no
significant differences in complications or hospital stays, supporting them as efficient
alternatives in modern healthcare [39]. The convergence of robotic systems with ultrasound
(RUS) imaging represents a significant technological advancement with far-reaching
implications for medical procedures, notably breast biopsies [40]. Statistical data underscores
their remarkable success, with RUS-guided breast biopsies achieving a striking success rate of
over 92% [40]. This high degree of precision ensures accurate breast tissue sampling, reducing
the likelihood of errors and missed diagnoses.
Furthermore, integrating robotics into ultrasound-guided procedures alleviates operator fatigue,
enhancing safety and improving overall efficiency. Patients benefit from reduced discomfort,
shorter procedure times, and minimized risks of complications. The overarching impact is
reflected in breast cancer diagnosis, where early detection rates have surged by up to 35% [40].
Integrating robotics into healthcare, especially in percutaneous procedures like biopsies, has
significantly improved precision. Recent statistics show that robotic guidance has led to over
90% accuracy in biopsies [41]. Robotic systems standardize procedures, reduce operator-
dependent variability, and speed up diagnostic processes. Patients experience minimal trauma,
faster recovery, and reduced scarring [42].
The robotic pill, a cutting-edge innovation in healthcare technology, offers a promising solution
for the noninvasive sampling of biomarkers, particularly in the challenging terrain of the
gastrointestinal (GI) tract, spanning over 9 meters [44]. Each pill capable of absorbing up to 30.7
mg of solution ensures precise and selective capture of biomarkers, making it a game-changer in
early disease detection [44]. By minimizing the need for invasive procedures, the robotic pill
promises to provide valuable insights into disease progression, early diagnosis, and personalized
treatment options, ushering in a new era of patient-friendly and effective healthcare solutions.
Microscale robots, encompassing capsule robots and microrobots, are significantly impacting
gastroenterology, especially concerning biopsy and pathogen collection within the
gastrointestinal (GI) tract [45].
With approximately 40 million clinic visits annually for GI diseases in the United States alone,
the significance of improved diagnostic and treatment methods cannot be overstated. Moreover,
GI cancers accounted for 32% of all cancer deaths in 2020. Early diagnosis and precise tissue
sampling are crucial for improving patient outcomes. Miniature robotic systems, like capsule
robots, have introduced noninvasive biopsy techniques that substantially enhance patient comfort
[46]. These robots equipped with retractable needles or forceps have the potential to reduce the
discomfort associated with invasive surgical procedures significantly. The steps of action of
these robots are shown in Fig.1. They contribute to increasing the 5-year survival rates for GI
cancers, such as rectal cancer, from as low as 20% for late diagnoses to 90% for early detection
[47].
Furthermore, microrobots with microgrippers or rotating blades are highly effective in collecting
tissue samples. Their ability to precisely localize and sample lesions profoundly impacts early
disease detection and diagnosis. These robots also play a vital role in capturing pathogens, such
as bacteria, in the GI tract, contributing to research on microbial infections and targeted
treatment strategies. The remote operation capabilities of these microrobots, along with their
real-time monitoring capabilities, not only enhance patient.

Fig. 1. Steps of Capsule Robot with retractable needle for Biopsy and Pathogen Collection [11].

4.6 Tissue penetration and microsurgery

Micro-robots have shown remarkable potential in tissue penetration and microsurgery, offering
innovative solutions to address complex challenges in medical procedures. These tiny robots,
often untethered and soft, possess unique advantages due to their compliant motions and
dexterity in handling delicate objects. They excel in navigating through intricate anatomical
structures with varying geometries and dimensions, adapting to rapidly changing physiological
conditions and unforeseen biological events [37]. For instance, some micro-robots can be
actuated using ultrasonic power through mechanisms like acoustic droplet vaporization-ignition,
allowing them to rapidly change from liquid to gas and generate thrust in a bullet-like manner.
This high-speed capability is invaluable for applications such as ablation and deep tissue
penetration. Additionally, implantable micro-robots, guided by magnetic fields or other means,
have been developed for ophthalmologic and ocular surgery, offering precise and minimally
invasive interventions within sensitive eye structures [48].
With their miniature size and specialized capabilities, Microrobots are finding increasingly
valuable applications in tissue penetration and microsurgery. Statistical data from studies
indicate their potential to address the challenges associated with delicate tissue manipulation and
surgical precision. For instance, in a systematic review of surgical tool-tissue forces, micro
robotic-assisted procedures demonstrated an average force exertion significantly lower than
traditional surgical methods [50]. These microrobots, often inspired by natural organisms, excel
in minimizing tissue damage, exerting precise and controlled forces, and navigating through
intricate anatomical structures. The data show microrobots are particularly beneficial in
procedures involving sensitive areas such as the brain or retina, where maneuverability and
precision shine.

Furthermore, their incorporation of various sensors and feedback mechanisms results in

enhanced surgical accuracy and safety, making them a promising tool for the future of
microsurgery [51]. As this technology advances, these statistical findings underscore the
transformative potential of microrobots in improving surgical outcomes and reducing the
associated risks. These tiny robotic marvels, inspired by natural organisms, have demonstrated
remarkable potential in addressing the intricate challenges associated with delicate tissue
manipulation and surgical precision. Statistical data from studies underscore their significance,
revealing that micro-robotic-assisted procedures substantially reduce the average force exerted
compared to traditional surgical methods. For instance, in a systematic review focusing on
surgical tool-tissue forces, microrobots have showcased their ability to generate an average
penetration force of 410 mN, a remarkable 22.7-fold increase compared to similar magnetically
guided needles with over 20 times smaller volume. Such data highlights the immense promise of
microrobots in scenarios requiring tissue penetration, including biopsy, suturing, cutting, drug
delivery, and access to deep-seated regions within complex organ structures such as the eye.
These robots, guided by magnetic fields and equipped with sophisticated sensors and feedback
mechanisms, ensure precise and controlled surgical maneuvers, enhancing accuracy and safety
[52]. As these advancements continue, the statistical evidence reinforces the transformative
potential of microrobots in elevating surgical outcomes while mitigating associated risks.
Microrobots hold immense potential for advancing the field of tissue penetration and
microsurgery in the context of head and neck cancers. These miniature robotic systems can offer
precise and minimally invasive access to delicate and hard-to-reach areas within the upper
aerodigestive tract. By incorporating microrobots into transoral procedures like Transoral
Robotic Surgery (TORS), surgeons can enhance their tissue manipulation and excision
capabilities. Using microrobots allows for greater control and dexterity, reducing the risk of
collateral tissue damage and improving the overall precision of surgical interventions. Statistical
data from recent studies demonstrates the promise of microrobotic technology, showcasing its
potential to revolutionize the treatment of head and neck cancers by providing safer and more
effective surgical options [53]. As these microrobotic systems continue to evolve and gain wider
acceptance, they have the potential to improve patient outcomes and minimize the long-term
impact of these complex cancer surgeries.

Microbots hold great promise in tissue penetration and microsurgery, addressing inherent
challenges in these delicate medical procedures. As described in the research paper, endonasal
endoscopic surgery (EES) involves complex tasks such as suturing within a limited workspace,
where precision is paramount. The application of microrobots can significantly enhance the
dexterity required for such procedures. While the paper primarily focuses on a robot-assisted
stitching method, it exemplifies the potential of microrobots in reducing tissue trauma and
improving the success rate of procedures. According to the study, the robot-assisted mode
demonstrated a remarkable success ratio of 65.3%, a substantial improvement over manual
operation (25.4%) [54]. This suggests that microrobots, with their enhanced dexterity and
precision, can play a pivotal role in optimizing tissue penetration and microsurgical tasks,
ultimately leading to better patient outcomes in head and neck cancer treatments and other
related procedures.

5. Challenges and Future Directions:

The development of microrobots in minimally invasive surgery holds tremendous promise but is
accompanied by significant challenges [55]. One primary obstacle is achieving efficient
propulsion within the human body, where microrobots must navigate intricate networks of blood
vessels and tissues. While various propulsion methods, such as chemical substrate-based
micromotors and external energy sources like magnetism, ultrasound, thermal, and electrical
energy, have been explored, further refinement is necessary for optimal performance. The
precise control and direction of microrobots, especially in dynamic and complex environments,
pose a substantial challenge. Progress has been made in MRI-based navigation systems and
electromagnetic control, but achieving the necessary level of maneuverability remains a hurdle.

Additionally, ensuring biocompatibility, safety, and the ability of microrobots to biodegrade after
completing their missions are vital for their practical application. In the future, microrobots can
revolutionize surgery by enabling targeted interventions at the cellular level, direct drug delivery
to diseased cells, and precise microsurgeries. However, rigorous research, extensive clinical
trials, and innovative technological advancements will be essential to overcome these challenges
and fully harness the potential of microrobotic surgery to enhance patient outcomes [55].

In microrobotics, particularly those driven by light, there are exciting opportunities and notable
challenges [56]. A major challenge stems from the limited driving force of optical manipulation,
which restricts the effective control of larger or heavier microrobots. Moreover, the complex and
costly equipment required for optical micromanipulation techniques hinders their widespread
adoption. Researchers are exploring alternative methods like Dielectrophoresis (DEP) to address
these issues to operate larger and heavier microrobots with increased driving forces. Another
challenge lies in the spatial control limitations of light, especially in three-dimensional space,
when compared to other control mechanisms such as magnetic or acoustic control. Overcoming
this limitation will necessitate innovative solutions and possibly hybrid approaches that combine
the strengths of multiple control methods.
Additionally, carefully considering the biocompatibility and toxicity of materials used in light-
powered microrobots is essential, particularly in biomedical applications. Future directions for
microrobots may include developing novel materials with superior mechanical and chemical
properties, advancements in shaping light beams, improvements in automatic algorithms and
control software, and innovative strategies for navigating through opaque media like blood. As
researchers continue to address these challenges, the potential for light-powered microrobots in
diverse applications, including medicine and environmental remediation, remains promising,
with the prospect of exciting developments in the field [56].
6. Conclusion:
 Summary of the key findings and contributions of bio-inspired micro-robotics to the field
of medicine.
 Emphasis on the potential to revolutionize medical procedures, improve patient
outcomes, and enhance the overall quality of healthcare.

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