Nano- and Microrobotics

Acting Part I: Actuators and manipulators (Manipulation at small scales)

Prof. Dr. Berna Özkale Edelmann
Garching, 28.11.2023
Nano- and microrobotics
Intelligent machines that can sense, think, and act.

Sensing Acting
Biosensing Nano- and Locomotion
Localization microrobotic Manipulation
systems

Processing
Control via external agents
Powering

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Manipulation at nano- and microscale

Task driven nano/microrobots Nanomanipulators

Cargo carriers, grippers, Scanning tunneling

bioactuators, active microcopy, atomic force
endoscopes microscopy, optical tweezers,
microfluidic tools

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Manipulation at nano- and microscale

Task driven nano/microrobots Nanomanipulators

Cargo carriers, grippers, Scanning tunneling

bioactuators, active microcopy, atomic force
endoscopes microscopy, optical tweezers,
microfluidic tools

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Robotic manipulation at small scales

Nano- and microrobotic manipulation entails small scale actions that are challenging to perform with
macroscale approaches
• Transportation and delivery
⎼ Therapeutics,
⎼ Particles,
⎼ Chemicals,
⎼ Cells...

• Mechanical perturbation
⎼ Minimally invasive surgery,
⎼ Force application to cells,
⎼ Local biopsy…

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Carrying and delivering cargo in microscale
A magnetically controlled microrobot (via magnetic torque) is used to select and deliver protein
crystals to the extraction site.
An electromagnetic coil system with 8 solenoids provides
5DOF control over magnetic microrobots wirelessly in 3D
space.

S. Schuerle, S. Erni, M. Flink, B. E. Kratochvil and B. J. Nelson, IEEE Transactions on Magnetics,

H. Tung, R. Pieters, D. F. Sargent and B. J. Nelson, 2014 IEEE ICRA, 2014, pp. 2092-2092.
vol. 49, no. 1, pp. 321-330, Jan. 2013.

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Carrying and delivering cargo in microscale
Optoelectronic tweezer based microrobot is able to grab, transport, and deliver cargo wirelessly.
Difficult tasks such as single cell isolation can be performed using these optically controlled micron
scale cargo carriers.

S. Zhang et al, PNAS 2019, 116 (30) 14823-14828. Wu, M. Optoelectronic tweezers. Nature Photon 5, 322–324 (2011)

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Carrying and delivering cargo in microscale
Optoelectronic tweezer driven microrobots are advantageous because they can achieve 50% more
force output (up to 400 nN).

S. Zhang et al, PNAS 2019, 116 (30) 14823-14828.

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Carrying and delivering cargo in microscale
The soft microgripper is controlled using two actuation strategies. The NIR laser activates gripping
while magnetic fields is used to guide motion. Forces up to 400 µN can be generated and the
microgripper can lift 1000 times more than its own weight!

Microgripper transports micro-

tissues in physiological
environment.

Jia, H., Mailand, E., Zhou, J., Huang, Z., Dietler, G., Kolinski, J. M., Wang, X., Sakar, M. S., Small 2019, 15, 1803870.

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Carrying and delivering cargo in microscale
In some cases, the material that the microrobot is manufactured from is directly used to perform a
specific action. An example is the metal-organic framework (MOF) micromotor which is able to
remove radioactive materials.

Yulong Ying, Amir Masoud Pourrahimi, Zdeněk Sofer, Stanislava Matějková, and Martin
Pumera ACS Nano 2019 13 (10), 11477-11487
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Carrying and delivering cargo in nanoscale
Magnetic nanoswimmers capable of optical trapping is used to transport colloidal particles and small
bacteria.

These nanorobots benefit from two

actuation modalities, can you tell
which ones?

Souvik Ghosh, Ambarish Ghosh, “Mobile nanotweezers for active colloidal manipulation” SCIENCE ROBOTICS, 2018 (3) eaaq0076
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Mechanically probing biological environments
In native tissue, cells reside in a complex 3D network of biopolymers which is inherently dynamic.
Physical changes in the extracellular matrix heavily influence cell behavior and microrobotic systems
can be used to investigate these fundamental interactions.

Griffith, L., Swartz, M. Capturing complex 3D tissue physiology in vitro. Nat Fazil E. Uslu et al, Adv. Mater. 2021, 2102641, DOI:
Rev Mol Cell Biol 7, 211–224 (2006) 10.1002/adma.202102641

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Mechanically probing biological environments
Optically triggered microactuators generate 10 µN force which is sufficient to actuate microtweezers
or microcompressors. The microdevices are specifically designed for mechanobiology applications.

Force magnitude and frequency is

controlled over many cycles by
turning NIR laser on and off
repeatedly.

Berna Özkale et al, “Modular soft robotic microdevices for dexterous biomanipulation”, Lab Chip, 2019,19, 778-788
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Mechanically probing biological environments
Active miniaturized endoscopes are particularly interesting for minimally invasive surgical procedures. A microcatheter system
is magnetically controlled to perform bronchoscopy in a phantom. A novel feedback control method omits the need for device
localization.

Janis Edelmann, Andrew J. Petruska, Bradley J. Nelson, “Estimation-Based Control of a Magnetic Endoscope without Device Localization”
Journal of Medical Robotics Research, 2018 (03) 1850002
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Mechanically probing biological environments
Optoelectromechanical small scale device is engineered for minimally invasive tissue ablation. The milli-device is 6 mm by 12
mm, can generate and deliver laser beams at 1.2 kHz speed with 10 DOF at 200 µm spatial resolution.

The optoelectromechanical microrobotic

device is integrated into an endoscope
and colonoscopy with tissue ablation is
simulated in a synthetic model.

Peter A. York, Rut Peña, Daniel Kent, Robert J. Wood, “Microrobotic laser steering for minimally invasive surgery” Science Robotics 2021 (6)
eabd5476 15
Manipulation at nano- and microscale

Task driven nano/microrobots Nanomanipulators

Cargo carriers, grippers, Scanning tunneling

bioactuators, active microcopy, atomic force
endoscopes microscopy, optical tweezers,
microfluidic tools

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Manipulating atoms
A boy and his atom: the world’s shortest movie by IBM

IBM, Switzerland
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Surface probe microscopy

Scanning probe microscopy based nanomanipulation involves the interaction between an externally
controlled probe and the surface of a small object.
• Surface-probe interactions can be electrical, mechanical, magnetic, fluidic, and thermal.
• Most commonly used nanomanipulation methods are
⎼ Scanning tunneling microscopy
⎼ Atomic force microscopy

Bian, K., Gerber, C., Heinrich, A.J. et al. Scanning probe microscopy. Nat Rev Methods Primers 1, 36 (2021).

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Scanning tunneling microscopy

When an atomically sharp metal tip get very close to a conductive surface,
• Electrons jump!
⎼ In quantum mechanics this is referred to as the tunneling effect
⎼ Tip-surface proximity ~ 0.3 to 1 nm
⎼ Biased voltage between tip and sample necessary

Bian, K., Gerber, C., Heinrich, A.J. et al. Scanning probe microscopy. Nat Rev Methods Primers 1, 36 (2021).

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Tunneling effect

Quantum mechanics dictate that an electron will behave both like a particle and a wave
• An electron bumps into an energy barrier
• Electron wavefunction decays and partially transmits
• Tunneling through the barrier

Transmission probability of an electron through the barrier

#%
(𝑒 !" − 𝑒 #!" )$ 𝑉, potential energy of the barrier
𝑇 = 1+
16𝜀(1 − 𝜀) 𝐸, energy of the electron
%⁄$ 𝑚! , mass of the electron
𝜅 = 2𝑚& 𝑉 − 𝐸 /ℏ$
𝐿, barrier distance
𝜀 = 𝐸 ⁄𝑉 ℏ, reduced Planck’s constant

Physical Chemistry by Peter Atkins and Julio de Paula, Oxford University Press, 8th edition

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Tunneling effect

Transmission probability of an electron decreases exponentially with increasing barrier thickness and
electron mass.
• Implications in scanning tunneling microscopy*
⎼ Tip-sample distance increases by 0.1 nm
⎼ Tunneling current decreases by 10 times

*Bian, K., Gerber, C., Heinrich, A.J. et al. Nat Rev Methods Primers 1, 36 (2021). Physical Chemistry by Peter Atkins and Julio
de Paula, Oxford University Press, 8th edition

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Instrumentation in STM

Nanoscale raster-scan is achieved with

• Very sharp tip (e.g. platinum, iridium wire)
• Piezoelectric materials for 3D scanners
• High mechanical resonance frequencies (1-5 kHz)
• Very low noise
⎼ Minimize vibrations (floating concrete blocks)
⎼ Thermal noise (operation at 5K in ultra-high vacuum)

Bian, K., Gerber, C., Heinrich, A.J. et al. Scanning probe microscopy. Nat Rev Methods Primers 1, 36 (2021). 22
STM applications in chemistry

Fabricating 20 atom long gold

nanochains on a NiAl (110) surface Running
chemical
reactions at
atomic scale

Detecting isomers of a chemical

N. Nilius, T. M. Wallis, W. Ho, Science, 2002 (297) 1853-1855. Bian, K., Gerber, C., Heinrich, A.J. et al. Nat Rev Methods
Primers 1, 36 (2021).

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Atomic force microscopy

Unlike STM, AFM relies on measuring forces at nanoscale

• Applicable to non-conductive surfaces and biological materials
• Environmental conditions possible
• An elastic cantilever with a sharp tip exerts force on a surface
⎼ Cantilever deflection is measured by a laser
⎼ Force-feedback is used map the surface
• Instrumentation requires
⎼ Piezoelectric scanners
⎼ Vibrational isolation
⎼ Raster-scanning

Bian, K., Gerber, C., Heinrich, A.J. et al. Scanning probe microscopy. Nat Rev Methods Primers 1, 36 (2021).

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Atomic force microscopy
Repulsive and attractive forces between the tip and the surface are observed during AFM operation. For each single point in
an AFM scan, an individual force-distance curve is measured. This allows detailed information about the mechanical
properties of the surface in question.

Bian, K., Gerber, C., Heinrich, A.J. et al. Scanning probe microscopy. Nat Rev Methods Primers 1, 36 (2021).

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AFM applications in biology

Force spectroscopy of single cells using atomic force microscopy. Nat Rev Methods Primers 1, 64 (2021). https://doi.org/10.1038/s43586-021-00067-6

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AFM to probe biological processes

Bian, K., Gerber, C., Heinrich, A.J. et al. Scanning probe microscopy. Nat Rev Methods Primers 1, 36 (2021).
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Optical tweezers

Dielectric particles subjected to a strong focused light beam will move towards the focal point due to
a gradient force.
• Requires a focused Gaussian laser beam
⎼ Very small focal point
⎼ Highest possible optical gradient
• Light microscope
⎼ Objectives with high numerical aperture

Molecular Biology of the Cell by B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, 5th Ed. 28
Forces in an optical trap

Forces acting on an optical trap depend on the particle size

• Particle is smaller than the wavelength of light (a)
⎼ Particle is polarized and moves towards high intensity gradient (𝐹()*+,&-. )

⎼ Particle simultaneously experiences a force due to absorption and scattering of light (𝐹/0*..&),-( )

• Particle is much larger than the wavelength of light (b)

⎼ Particle refracts or reflects light
⎼ Change in momentum in light and particle
⎼ 𝐹)&1)*0.&+ pulls particle toward focal point
⎼ 𝐹)&12&0.&+ pushes particle forward

Bustamante, C.J., Chemla, Y.R., Liu, S. et al. Optical tweezers in single-molecule biophysics. Nat Rev Methods Primers 1, 25 (2021).

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Types of optical tweezers
Optical tweezers can be used to apply force or torques to biomolecules and cells. Moreover,
fluorescence imaging tools can be coupled with optical traps for quantitative measurements at
nanoscale.

Bustamante, C.J., Chemla, Y.R., Liu, S. et al. Optical tweezers in single-molecule biophysics. Nat Rev Methods Primers 1, 25 (2021).
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Live cell manipulation
Holographic optical tweezers have been engineered to move and organize single cells in distinct
patterns for tissue engineering purposes.

Mouse embryonic stem cells are assembled into

different 3D patterns. Cells are fluorescently labeled
(green) to monitor their healthy.

Kirkham, G., Britchford, E., Upton, T. et al. Sci Rep 5, 8577 (2015). https://doi.org/10.1038/srep08577

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Magnetic tweezers
Magnetic field gradient induced force on a magnetic particles can be used to manipulate biomolecules such as
enzymes, DNA, and ATP nanomotors.
• High magnetic field gradients
⎼ Sharp electromagnetic tips
⎼ Small permanent magnets
• Microscope setup
• Particle size ~ 0.5 – 5 µm
• Biological applications
⎼ Investigating the structure of DNA
⎼ pN forces

Neuman, K., Nagy, A. Single-molecule force spectroscopy: optical tweezers, magnetic tweezers and atomic force microscopy. Nat
Methods 5, 491–505 (2008).
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Microfluidic manipulation

Miniaturizing chemical processes into microscale channels

• Two immiscible liquids meet at a microscale junction
• Pinching off of droplets
• Advantages
⎼ Large sample volume, high-throughput processing, low reagent costs…
• Biomedical applications
⎼ Drug discovery and organ-on-chip applications…

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Microfluidic biomanipulation

Microfluidic devices are particularly appealing for biomedical applications

• Drug discovery, cell delivery, and organ-on-chip …

High-throughput sample analysis Therapeutic cell delivery

Duncombe, T., Tentori, A. & Herr, A. Microfluidics: reframing biological enquiry. Nat Mao, A., Shin, JW., Utech, S. et al. Nature
Rev Mol Cell Biol 16, 554–567 (2015). Mater 16, 236–243 (2017).

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A brief comparison of nanomanipulators
The acting capability (e.g. generated force) of a nano-bio-manipulator depends on the chosen
manipulation strategy.

Neuman, K., Nagy, A. Single-molecule force spectroscopy: optical tweezers, magnetic tweezers and atomic force microscopy. Nat
Methods 5, 491–505 (2008).
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Manipulation at nano- and microscale

Task driven nano/microrobots Nanomanipulators

Cargo carriers, grippers, Scanning tunneling

bioactuators, active microcopy, atomic force
endoscopes microscopy, optical tweezers,
microfluidic tools

36
Nano- and microrobotics
Intelligent machines that can sense, think, and act.

Sensing Acting
Biosensing Nano- and Locomotion
Localization microrobotic Manipulation
systems

Processing
Control via external agents
Powering

37
Reading list
• Book chapter:
⎼ Chapter 4, “Quantum Nature of the Nanoworld”, from Nanopysics and Nanotechnology by Edward L. Wolf

• Review article:
⎼ “Trends in Micro-/Nanorobotics: Materials Development, Actuation, Localization, and System Integration for Biomedical
Applications” by B. Wang, K. Kostarelos, B. J. Nelson, L. Zhang, Adv. Mater. 2021, 33, 2002047.
⎼ Relevant for the next several weeks

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