Jaideep Katuri1,2, Xing Ma2,3, Morgan M Stanton2, Samuel Sánchez1,2,4. 1. Institute for Bioengineering of Catalonia (IBEC) , Baldiri i Reixac 10-12, 08028 Barcelona, Spain. 2. Max-Planck-Institut für Intelligente Systeme , Heisenbergstr. 3, D-70569 Stuttgart, Germany. 3. School of Materials Science and Engineering, Harbin Institute of Technology Shenzhen Graduate School , 518055 Shenzhen, China. 4. Institució Catalana de Recerca i Estudis Avancats (ICREA) , Pg. Lluís Companys 23, 08010 Barcelona, Spain.
Abstract
Self-propelled colloids have emerged as a new class of active matter over the past decade. These are micrometer sized colloidal objects that transduce free energy from their surroundings and convert it to directed motion. The self-propelled colloids are in many ways, the synthetic analogues of biological self-propelled units such as algae or bacteria. Although they are propelled by very different mechanisms, biological swimmers are typically powered by flagellar motion and synthetic swimmers are driven by local chemical reactions, they share a number of common features with respect to swimming behavior. They exhibit run-and-tumble like behavior, are responsive to environmental stimuli, and can even chemically interact with nearby swimmers. An understanding of self-propelled colloids could help us in understanding the complex behaviors that emerge in populations of natural microswimmers. Self-propelled colloids also offer some advantages over natural microswimmers, since the surface properties, propulsion mechanisms, and particle geometry can all be easily modified to meet specific needs. From a more practical perspective, a number of applications, ranging from environmental remediation to targeted drug delivery, have been envisioned for these systems. These applications rely on the basic functionalities of self-propelled colloids: directional motion, sensing of the local environment, and the ability to respond to external signals. Owing to the vastly different nature of each of these applications, it becomes necessary to optimize the design choices in these colloids. There has been a significant effort to develop a range of synthetic self-propelled colloids to meet the specific conditions required for different processes. Tubular self-propelled colloids, for example, are ideal for decontamination processes, owing to their bubble propulsion mechanism, which enhances mixing in systems, but are incompatible with biological systems due to the toxic propulsion fuel and the generation of oxygen bubbles. Spherical swimmers serve as model systems to understand the fundamental aspects of the propulsion mechanism, collective behavior, response to external stimuli, etc. They are also typically the choice of shape at the nanoscale due to their ease of fabrication. More recently biohybrid swimmers have also been developed which attempt to retain the advantages of synthetic colloids while deriving their propulsion from biological swimmers such as sperm and bacteria, offering the means for biocompatible swimming. In this Account, we will summarize our effort and those of other groups, in the design and development of self-propelled colloids of different structural properties and powered by different propulsion mechanisms. We will also briefly address the applications that have been proposed and, to some extent, demonstrated for these swimmer designs.
Self-propelled colloids have emerged as a new class of active matter over the past decade. These are micrometer sized colloidal objects that transduce free energy from their surroundings and convert it to directed motion. The self-propelled colloids are in many ways, the synthetic analogues of biological self-propelled units such as algae or bacteria. Although they are propelled by very different mechanisms, biological swimmers are typically powered by flagellar motion and synthetic swimmers are driven by local chemical reactions, they share a number of common features with respect to swimming behavior. They exhibit run-and-tumble like behavior, are responsive to environmental stimuli, and can even chemically interact with nearby swimmers. An understanding of self-propelled colloids could help us in understanding the complex behaviors that emerge in populations of natural microswimmers. Self-propelled colloids also offer some advantages over natural microswimmers, since the surface properties, propulsion mechanisms, and particle geometry can all be easily modified to meet specific needs. From a more practical perspective, a number of applications, ranging from environmental remediation to targeted drug delivery, have been envisioned for these systems. These applications rely on the basic functionalities of self-propelled colloids: directional motion, sensing of the local environment, and the ability to respond to external signals. Owing to the vastly different nature of each of these applications, it becomes necessary to optimize the design choices in these colloids. There has been a significant effort to develop a range of synthetic self-propelled colloids to meet the specific conditions required for different processes. Tubular self-propelled colloids, for example, are ideal for decontamination processes, owing to their bubble propulsion mechanism, which enhances mixing in systems, but are incompatible with biological systems due to the toxic propulsion fuel and the generation of oxygen bubbles. Spherical swimmers serve as model systems to understand the fundamental aspects of the propulsion mechanism, collective behavior, response to external stimuli, etc. They are also typically the choice of shape at the nanoscale due to their ease of fabrication. More recently biohybrid swimmers have also been developed which attempt to retain the advantages of synthetic colloids while deriving their propulsion from biological swimmers such as sperm and bacteria, offering the means for biocompatible swimming. In this Account, we will summarize our effort and those of other groups, in the design and development of self-propelled colloids of different structural properties and powered by different propulsion mechanisms. We will also briefly address the applications that have been proposed and, to some extent, demonstrated for these swimmer designs.
Micromotors are small autonomous devices
that are capable of performing
complex tasks in fluidic environments. Since their first demonstration
in 2004, there have been significant advances in terms of developing
new propulsion mechanisms and in incorporating methods of motion control.
The efforts to gain a deeper understanding of the physical mechanisms
involved and attempts to use these micromotors in industrial and biomedical
processes have largely occurred in parallel.Among the first
artificial micromotors developed were the bimetallic
rods of Au–Pt, which propelled in a solution of H2O2 due to electrokinetic forces setup by the preferential
oxidation of the peroxide on the Pt side and the reduction on the
Au side.[1,2] Later on, two other geometries were demonstrated
in spherical swimmers half coated with a metal catalyst to enable
self-phoresis[3] and tubular structures,
which had the catalyst on the inside and propelled due to the expulsion
of oxygen bubbles.[4] Since then, a number
of new propulsion methods have been developed for these micromotors
including those based on photochemical, ultrasound, and thermophoretic
mechanisms.[5] This range of geometries and
propulsion mechanisms allows for a wide range of applications from
biosensing and drug delivery to environmental remediation.[6−12]A major drawback, nevertheless, has been the toxicity of the
fuel,
making difficult the implementation of micromotors in biological systems.
This challenge has been addressed by developing zinc and magnesium
based micromotors, which can propel in nontoxic fuels or fuel free
micromotors driven by light or magnetic fields.[13−16] Recent efforts have also focused
on developing bubble-free enzyme based motors that derive their propulsion
from biocompatible substrates, and biohybrid micromotors whose propulsion
is driven by natural microswimmers such as sperms and bacteria. The
flexibility that researchers have in controlling the physical properties
of the micromotors makes them promising tools for a number of applications.
Tubular
Bubble Propelled Microjets
Artificial microjets, based on
microtubular geometries self-propel
by the ejection of a jet of bubbles. These structures are fabricated
by two main methods, roll-up nanotechnology[4,17] and
electrodeposition using porous templates.[18,19] Both methods incorporate a catalyst in the interior that decomposes
the chemical substrate into gas bubbles (e.g., O2 or H2) (Figure A).[20,13] The microjets also require surfactants within
the solution to reduce the surface tension in the tubular confinement,
facilitating the stability and the release of bubbles.[21,22] The curvature and confinement of the microtube is crucial for the
gas to accumulate and be used for propulsion.[23]
Figure 1
Fabrication
and control of tubular microjets. SEM image of (A)
a tubular microjet fabricated by the roll-up method, (B) a tubular
microjet fabricated by electrodeposition method, and (C) a nanojet
synthesized based on heteroepitaxically grown layers. (D) Different
types of swimming behavior. (E) Folding and unfolding of thermoresponsive
microtubes leads to a variation in propulsion velocities. (F) An eight-coil
magnetic setup used for 3-D control of microjets. (G) Light regulated
velocity control of microjets. Panel A reprinted with permission from
ref (39). Copyright
2016 John Wiley and Sons, Inc. Panel C reprinted with permission from
ref (24). Copyright
2011 John Wiley and Sons, Inc. Panel D reprinted with permission from
ref (20). Copyright
2009 John Wiley and Sons, Inc. Panel E reprinted with permission from
ref (23). Copyright
2014 John Wiley and Sons, Inc. Panel G reprinted with permission from
ref (28). Copyright
2011 John Wiley and Sons, Inc. Panel F reprinted with permission from
ref (27). Copyright
2013 AIP Publishing.
Fabrication
and control of tubular microjets. SEM image of (A)
a tubular microjet fabricated by the roll-up method, (B) a tubular
microjet fabricated by electrodeposition method, and (C) a nanojet
synthesized based on heteroepitaxically grown layers. (D) Different
types of swimming behavior. (E) Folding and unfolding of thermoresponsive
microtubes leads to a variation in propulsion velocities. (F) An eight-coil
magnetic setup used for 3-D control of microjets. (G) Light regulated
velocity control of microjets. Panel A reprinted with permission from
ref (39). Copyright
2016 John Wiley and Sons, Inc. Panel C reprinted with permission from
ref (24). Copyright
2011 John Wiley and Sons, Inc. Panel D reprinted with permission from
ref (20). Copyright
2009 John Wiley and Sons, Inc. Panel E reprinted with permission from
ref (23). Copyright
2014 John Wiley and Sons, Inc. Panel G reprinted with permission from
ref (28). Copyright
2011 John Wiley and Sons, Inc. Panel F reprinted with permission from
ref (27). Copyright
2013 AIP Publishing.Electrodeposited microjets are smaller (L ≈
5–10 μm) (Figure B) than rolled-up microjets (L ≈ 25–500
μm) and present a relative speed (body length (bl)·s–1) larger than those observed in rolled-up tubes for
the same concentration of fuel, reaching a maximum speed of 2400 μm
s–1 in 5 wt % H2O2.[18] High-strain engineering with epitaxial growth
of nanomembranes can lead to nanojets of extremely small sizes, down
to 280 nm in diameter (Figure C).[24]The direction of motion
of microjets cannot be, a priori, predicted.
Small asymmetries can change the angle at which the bubbles are released,
which contributes to a torque leading to trajectories of different
shapes and speeds (Figure D,E).[25,26] To control their directionality
in 3D,[27] various methods using magnetic
fields, ultrasound, temperature, light, and chemical gradients have
been presented (Figure , panels F[27] and G[28]) (see ref (6) and references therein).The bubble-propelled microjets can
swim in high ionic media unlike
self-ionic diffusiophoretic and electrokinetic swimmers and in several
different media, types of water, serum, and reconstituted blood (see
ref (6) and references
therein). Yet, small changes in viscosity of the medium affect the
dynamics of the microjets. Their motion in reconstituted blood was
hindered at 25 °C but was regained at physiological temperature,
which reduced the viscosity of the media.[29,30]Over the past few years, several proof-of-concept applications
of microjets have been reported, including the drilling of soft matter[25] (Figure G), transport of cargo and cells on-chip[31−33] (Figure F), biosensing,[34] and cleaning of polluted water.[35,36] However, the high concentration of H2O2 used
for the propulsion causes oxidative stress, damaging and killing the
cells. To address this limitation, more efficient and biocompatible
means of propulsion are being developed. The use of enzymes[37] or motile cells[38] could give rise to biologically friendly micromotors and will be
discussed in a later section.
Figure 2
Environmental and biomedical
applications of microjets. (A) Schematic
for the degradation of polluted water (Rh6G) into inorganic products.
(B) Scheme of graphene-oxide (GOx) microbots for lead decontamination
and recovery. (C) Degradation of Rh6G (blue diamonds). Black dots
and squares are controls. (D) Removal of lead by GOx micromotors.
(E) Lifetime activity of microjets for 24 h. (F) SEM (A) and optical
(B) images of a microjet with CAD cells. (G) Optical microscopy image
of a nanotool drilling into a HeLa cell. Scalebar represents 10 μm.
Panels A and C reprinted with permission from ref (35). Copyright 2013 American
Chemical Society. Panels B and D reprinted with permission from ref (40). Copyright 2016 American
Chemical Society. Panel G reprinted with permission from ref (25) Copyright 2012 American
Chemical Society. Panel F reproduced with permission from ref (31), 2010 Royal Society of
Chemistry.
Environmental and biomedical
applications of microjets. (A) Schematic
for the degradation of polluted water (Rh6G) into inorganic products.
(B) Scheme of graphene-oxide (GOx) microbots for lead decontamination
and recovery. (C) Degradation of Rh6G (blue diamonds). Black dots
and squares are controls. (D) Removal of lead by GOx micromotors.
(E) Lifetime activity of microjets for 24 h. (F) SEM (A) and optical
(B) images of a microjet with CAD cells. (G) Optical microscopy image
of a nanotool drilling into a HeLa cell. Scalebar represents 10 μm.
Panels A and C reprinted with permission from ref (35). Copyright 2013 American
Chemical Society. Panels B and D reprinted with permission from ref (40). Copyright 2016 American
Chemical Society. Panel G reprinted with permission from ref (25) Copyright 2012 American
Chemical Society. Panel F reproduced with permission from ref (31), 2010 Royal Society of
Chemistry.Recent works have demonstrated
that the bubbles released from the
microjets can mix solutions and enhance chemical reactions. Microjets
that use up H2O2 as a fuel and generate and
actively transport free radicals in the solution in a 3D manner boost
the degradation of organic dyes via Fenton-like reactions (Figure A,C). Long-term activity
was recorded for rolled-up microjets as they continuously generated
bubbles for 24 h (Figure E). These microjets can be reused over a couple of months
without significant reduction in performance.[39] Electrodeposited microjets containing graphene-oxide on the outside[41] have been reported as “heavy metal scrubbers”.[40] Pb is captured by graphene-modified microjets
and cleaned out from contaminated solutions. The metal can thereafter
be desorbed, and microjets can be reused again. (Figure B,D). These recent works demonstrate
that despite the challenges in using microjets for biomedical applications,
there is a possibility to use the chemical self-propulsion of microjets
for other industrial applications.
Spherical Phoretic Microswimmers
To understand the fundamental aspects of directed motion at the
micro- and nanoscale, spherical, phoretically propelled colloids have
been preferred due to both the ease of fabrication for experimental
studies and the convenience of modeling simpler geometries. In 2007,
it was demonstrated by Howse et al. that colloidal particles half
coated with Pt could undergo phoretic migration in local, self-generated
chemical gradients.[3] When these particles
are suspended in H2O2, the Pt half catalyzes
the degradation of the peroxide while the silica half remains inert.
This creates a gradient of the reaction product around the colloidal
particle in which the particle migrates. The exact details of the
propulsion mechanism are still under debate because recent experiments
suggested that the mechanism is perhaps more complex than the neutral
diffusiophoretic model that was originally used to explain this behavior.[42,43]Because of the microscale size of the Janus particles, they
are
subject to rotational diffusion due to thermal forces, which constantly
reorient them. A method to control the directionality of the particles
involves the use of out-of-plane magnetic layers together with catalytic
layers. (Figure A,B).[44,45] It was also shown that Janus colloids (Figure C) could pick up and transport cargo via
either magnetic or steric interactions (Figure D).[46]
Figure 3
Self-phoretic
Janus microswimmers. (A) SEM image of silica–Pt
Janus particles. (B) External magnetic fields to guide particles.
(C) Magnetic caps used to transport paramagnetic particles. (D) Transport
of cargo by single/double Janus particle configuration. Panels A and
C reproduced with permission from ref (44). Copyright 2012 American Chemical Society. Panel
B reproduced with permission from ref (45). Copyright 2015 Intech. Panel D reproduced with
permission from ref (46). Copyright 2011 Royal Society of Chemistry.
Self-phoretic
Janus microswimmers. (A) SEM image of silica–Pt
Janus particles. (B) External magnetic fields to guide particles.
(C) Magnetic caps used to transport paramagnetic particles. (D) Transport
of cargo by single/double Janus particle configuration. Panels A and
C reproduced with permission from ref (44). Copyright 2012 American Chemical Society. Panel
B reproduced with permission from ref (45). Copyright 2015 Intech. Panel D reproduced with
permission from ref (46). Copyright 2011 Royal Society of Chemistry.Since the Janus particles swim close to surfaces, additional
confinement
effects become relevant, leading to a rich behavior of swimming.[49] Recent studies have shown that a combination
of hydrodynamic, phoretic, and chemo-osmotic effects result in a stable
orientation of the particles near surfaces.[47,50] When the particles are suspended in water, they orient with their
caps facing the bottom surface due to the bottom heaviness induced
by the Pt cap. However, once H2O2 is added to
the system, introducing activity, they assume a stable orientation
that is parallel to the bottom surface (Figure A,B). It could also be shown, both experimentally
and via numerical simulations, that the presence of a second perpendicular wall has a similar
effect on the orientation of the particles. In proximity of a perpendicular
wall, which could be as small as 400 nm step (<0.2Rparticle), the particles tend to assume a stable orientation
that is parallel to both the bottom surface and the perpendicular
step (Figure C). This
allows for the development of intrinsic guidance systems that do not
rely on any external fields.
Figure 4
Self-phoretic Janus microswimmers near surfaces.
(A) Silica–Pt
Janus particles confined near a surface reorient on addition of H2O2. A second vertical step has similar effect.
(B) Phase portrait of a Janus particle near a surface showing the
steady-state at the cap-parallel position. (C) (a) Approach, reorientation,
and guiding of a Janus particle at a vertical 800 nm step. (b) Numerically
calculated steady-state distribution of the reaction products. (D)
Self-assembly of Janus microswimmers around an asymmetric gear. (E)
Dependence of angular velocity of the microgears on the number of
Janus particles. Panels A–C reproduced with permission from
ref (47). Copyright
2016 Nature Publishing Group. Panels D and E reproduced with permission
from ref (48). Copyright
2016 John Wiley & Sons, Inc.
Self-phoretic Janus microswimmers near surfaces.
(A) Silica–Pt
Janus particles confined near a surface reorient on addition of H2O2. A second vertical step has similar effect.
(B) Phase portrait of a Janus particle near a surface showing the
steady-state at the cap-parallel position. (C) (a) Approach, reorientation,
and guiding of a Janus particle at a vertical 800 nm step. (b) Numerically
calculated steady-state distribution of the reaction products. (D)
Self-assembly of Janus microswimmers around an asymmetric gear. (E)
Dependence of angular velocity of the microgears on the number of
Janus particles. Panels A–C reproduced with permission from
ref (47). Copyright
2016 Nature Publishing Group. Panels D and E reproduced with permission
from ref (48). Copyright
2016 John Wiley & Sons, Inc.The ability of Janus particles to align and move along steps
has
also been exploited to assemble multiple particles around a microfabricated
gear shaped structure, which has six asymmetric teeth and an external
radius of 8 μm (Figure D).[48] Initially the Janus particles
and the gears are suspended in water where they are randomly distributed.
Upon addition of H2O2, the particles begin to
self-propel while the passive gears remain inert. When a particle
approaches the gear, it aligns along the edge of the gear and depending
on the angle of incidence either leaves the gear or slides to the
corner where it gets stuck (Figure D(a–d)). The effect of the number of self-propelled
particles assembled around a gear and its angular velocity was also
studied. It could be shown that up to three particles, the angular
velocity increases on addition of new self-propelled particles. However,
an even greater number of particles results in lower angular velocities
probably owing either to the local depletion of fuel concentration
around the gear or the chemical gradient from adjacent particles resulting
in lower propulsion velocities (Figure E).
Swimming at the Nanoscale
Achieving
directional propulsion of nanomotors is challenging due
to the strong rotational diffusion at these length scales. The nanomotors
possess very short persistence length (L = τV, where τ is the rotational diffusion time and V is the ballistic velocity), which is difficult to observe
by optical microscopy techniques.[54] Usually,
the self-propelled nanomotors are characterized by the enhancement
of effective diffusion coefficient (Deff).A series of half-coated catalytic Janus mesoporous silica
nanomotors
with an average diameter of 40, 65, and 90 nm (Figure A, part a) could be propelled by the heterogeneous
catalytic reaction of H2O2 decomposition and
driven by a self-diffusiophoretic mechanism. Tracking trajectories
of these nanomotors (90 nm) demonstrated a larger diffusion in the
presence of H2O2 (blue and red) compared to
that without it (black) (Figure A, part b).[51] Another type
of nanomotor based on Au–Pt metals was fabricated by the glancing
angle deposition method (GLAD) with sizes of 30 or 60 nm. Their motion
mechanism was attributed to self-electrophoresis due to charge transfer
induced electric field (Figure B, part a). Dynamic light scattering (DLS) experiments showed
a fuel dependent “left-shift” behavior in the distribution
curve of the relaxation time of Au–Pt nanomotors (Figure B, part b), corresponding
to an enhancement of effective diffusion coefficient (Figure B, part c).[52] Nanomotors based on supramolecular self-assembly loaded
with Pt NPs (Figure C, part a) also show enhanced diffusion in the presence of H2O2 (Figure C, parts b and c). Nanoparticle tracking analysis (NTA) technology
was used for tracking of the nanomotors, and their motion was attributed
to a fast ejection of catalytic reaction products, for example, O2, from the small opening of the stomatocytes.[53]
Figure 5
Propulsion at nanoscale. (A) Janus mesoporous silica nanomotor:
(a) TEM image and schematic of the nanomotor, (b) tracking trajectories
and (c) MSD plots of the nanomotors. (B) Au–Pt nanomotor: (a)
schematic of the self-electrophoresis of Au–Pt nanomotor; DLS
measurement indicates (b) a left shift of relaxation time and (c)
enhancement of translational diffusion with increasing H2O2 concentration. (C) (a) Schematic of a stomatocytes
nanomotor, (b) MSD of the platinum-filled stomatocytes before and
after the addition of H2O2, and (c) size distribution
of platinum-filled stomatocytes before (blue) and after (red) the
addition of H2O2. Inset shows the same measurements
for stomatocytes without Pt. Panel A reprinted with permission from
ref (51). Copyright
2015 American Chemical Society. Panel B reprinted with permission
from ref (52). Copyright
2014 American Chemical Society. Panel C reprinted from ref (53) with permission. Copyright
2012 Nature Publishing Group.
Propulsion at nanoscale. (A) Janus mesoporous silica nanomotor:
(a) TEM image and schematic of the nanomotor, (b) tracking trajectories
and (c) MSD plots of the nanomotors. (B) Au–Pt nanomotor: (a)
schematic of the self-electrophoresis of Au–Pt nanomotor; DLS
measurement indicates (b) a left shift of relaxation time and (c)
enhancement of translational diffusion with increasing H2O2 concentration. (C) (a) Schematic of a stomatocytes
nanomotor, (b) MSD of the platinum-filled stomatocytes before and
after the addition of H2O2, and (c) size distribution
of platinum-filled stomatocytes before (blue) and after (red) the
addition of H2O2. Inset shows the same measurements
for stomatocytes without Pt. Panel A reprinted with permission from
ref (51). Copyright
2015 American Chemical Society. Panel B reprinted with permission
from ref (52). Copyright
2014 American Chemical Society. Panel C reprinted from ref (53) with permission. Copyright
2012 Nature Publishing Group.To move toward more biocompatible propulsion sources, there
has
been a recent effort to integrate enzymes in the nanomotors.[55] Enzymes trigger biocatalytic reactions, which
can convert chemical energy into kinetic motion for bioprocesses,
for example, intracellular protein transport. Researchers immobilized
catalase into “roll-up” microtubes providing efficient
bubble propulsion (about 10 times faster propulsion than with Pt catalyst)
by triggering the decomposition of H2O2 inside
the microjets (Figure A, part a).[37] A similar strategy has been
employed to power polymeric microtubes fabricated by template assisted
electrochemistry deposition[59] or layer-by-layer
self-assembly.[60] In smaller motors, catalase
was also recently conjugated onto one side of a Janus mesoporous silica
cluster, and its propulsion was driven by continuous generation of
O2 bubbles. (Figure A, part b).[56]
Figure 6
Enzyme-powered micro-
and nanomotors. (A) Bubble propulsion of
(a) tubular microjet and (b) Janus mesoporous cluster motor modified
with catalase. (B) Self-propulsion of Janus hollow mesoporous nanomotors
powered by various enzymes, catalase, urease, and glucose oxidase
(GOx). (C) Urease powered hollow capsule: (a) motion control by manipulating
the enzymatic activity, (b) “on”/“off”
motion control by addition of inhibitor and DTT, and (c) repeated
motion control up to 8 cycles. Panel A, part a, reproduced with permission
from ref (37). Copyright
2010 American Chemical Society. Panel A, part b, reprinted with permission
from ref (56). Copyright
2015 Royal Society of Chemistry. Panel B reproduced with permission
from ref (57). Copyright
2015 American Chemical Society. Panel C reprinted with permission
from ref (58). Copyright
2016 American Chemical Society.
Enzyme-powered micro-
and nanomotors. (A) Bubble propulsion of
(a) tubular microjet and (b) Janus mesoporous cluster motor modified
with catalase. (B) Self-propulsion of Janus hollow mesoporous nanomotors
powered by various enzymes, catalase, urease, and glucose oxidase
(GOx). (C) Urease powered hollow capsule: (a) motion control by manipulating
the enzymatic activity, (b) “on”/“off”
motion control by addition of inhibitor and DTT, and (c) repeated
motion control up to 8 cycles. Panel A, part a, reproduced with permission
from ref (37). Copyright
2010 American Chemical Society. Panel A, part b, reprinted with permission
from ref (56). Copyright
2015 Royal Society of Chemistry. Panel B reproduced with permission
from ref (57). Copyright
2015 American Chemical Society. Panel C reprinted with permission
from ref (58). Copyright
2016 American Chemical Society.One advantage of enzyme powered micro- or nanomotors is the
versatility
in choices of enzyme/fuel combinations. Janus structures of hollow
mesoporous silica nanoparticles were coupled with catalase, urease,
and glucose oxidase (GOx) to achieve propulsion (Figure B).[57] On a slightly larger scale, fuel dependent enhanced diffusion of
polystyrene microparticles fully coated with catalase or urease enzymes
has been reported.[61] Polymeric stomatocyte
nanoparticles were loaded with catalase and GOx, consuming glucose
to achieve self-propulsion via a cascade of enzymatic reactions.[62] Enzymes were able to power nanorods,[63] nanotubes,[64] and
Janus microparticles,[65] which all demonstrated
enhanced diffusion as well. These works have demonstrated the feasibility
of using biocompatible fuels, for example, urea and glucose, to power
micro- and nanomotors. Moreover, long-range directional propulsion
of enzymatic micromotors was recently reported for urease conjugated
Janus structures of mesoporous silica hollow particles (Figure C, part a).[58] These self-propelled microcapsules were powered by urease
triggered decomposition of urea at physiological concentrations. By
manipulating the enzymatic activity of urease by addition of inhibitors,
for example, Hg2+ or Ag+, the motors could also
be instantly stopped and, upon addition of the enzyme protection reagent
dithiothreitol (DTT), reactivated (Figure C, part b) for multiple cycles (Figure C, part c). Additionally,
incorporation of a magnetic element into the structure allows for
directional guidance. Bubble-free propulsion of enzyme-powered tubular
nanojets of 220 nm diameter and tunable lengths has been recently
reported.[64] Biocompatible tubular nanojets
and micro- and nanomotors hold great potential for active drug delivery in vitro and even in vivo.
Biohybrid Micromotors
Biohybrid motors focus on the interaction of a motile cell with
artificial materials to create a mobile system that is powered by
cellular actuation. Biohybrids are not powered by toxic chemical fuels
but by biological fluids, making them ideal for biomedical applications.
They are responsive to their local environment (pH, temperature, and
chemical gradients) and are capable of performing complex tasks that
synthetic-only motors would not be capable of. For a biohybrid powered
by a single flagellated cell, sperm are an optimal candidate. Sperm
are powerful microscale (50–70 μm long) cells that have
demonstrated directional guidance by chemotaxis, thermotaxis, and
rheotaxis and can alter their flagella beat when exposed to chemical
signals. For a sperm powered microbot, a single bull spermatozoon
was trapped within a fabricated microtube (20–50 μm)
(Figure A).[38] The partial penetration of the sperm into the
tube, allowed the flagellum to operate unhindered and push the tube
through a fluid with an average velocity of 5–30 μm/s
depending on the penetration depth, length of tube, and temperature.
The magnetic properties of the microtube allowed for external magnetic
guidance with a permanent magnet or an electromagnetic coil, and the
biohybrid could be directed through a microfluidic chamber.[66,67] Triggered release of sperm from biohybrids was achieved with the
thermoresponsive polymer poly(N-isopropylacrylamide)
(PNIPAM) incorporated into flexible microtubes,[68] by increasing the temperature of the solution above 28
°C forcing the polymer microtube tube to unroll. More recently,
a sperm biohybrid has been fabricated by capturing a sperm inside
a microhelix.[69] Using direct laser writing,[70] microhelices that were capable of swimming with
an applied rotating magnetic field were fabricated from a NiTi bilayer.
The rotating helix delivered and released the sperm to an oocyte wall,
suggesting the biohybrid’s applicability for infertility treatment.
However, the future of sperm biohybrids for fertilization applications
will require testing these biohybrids in in vivo environments
(Figure B).
Figure 7
Sperm and bacteria
powered biohybrids. (A) Bull spermatoozen trapped
within microtubes. (B) Sperm cell coupling (i), transport (ii), approach
to the oocyte membrane (iii), and release (iv). (C) MC-1 bacteria
with (bottom) and without liposomes (top). (D) Janus particles with
specific cell adhesion of E. coli to the metal cap.
(E) Beads (30 μm) with attached Serratia marcescens. (F) Examples of E. coli swimming with 2 μm
and 600 nm Janus particles. Panels A, D, and F reprinted with permission
from refs (38 and 76). Copyright
2016 John Wiley and Sons, Inc. Panel B reprinted with permission from
ref (69). Copyright
2016 American Chemical Society. Panel C reprinted with permission
from ref (72). Copyright
2014 American Chemical Society. Panel E reprinted with permission
from ref (75). Copyright
2012 Springer Science+Business Media, LLC.
Sperm and bacteria
powered biohybrids. (A) Bull spermatoozen trapped
within microtubes. (B) Sperm cell coupling (i), transport (ii), approach
to the oocyte membrane (iii), and release (iv). (C) MC-1 bacteria
with (bottom) and without liposomes (top). (D) Janus particles with
specific cell adhesion of E. coli to the metal cap.
(E) Beads (30 μm) with attached Serratia marcescens. (F) Examples of E. coli swimming with 2 μm
and 600 nm Janus particles. Panels A, D, and F reprinted with permission
from refs (38 and 76). Copyright
2016 John Wiley and Sons, Inc. Panel B reprinted with permission from
ref (69). Copyright
2016 American Chemical Society. Panel C reprinted with permission
from ref (72). Copyright
2014 American Chemical Society. Panel E reprinted with permission
from ref (75). Copyright
2012 Springer Science+Business Media, LLC.For multiflagellated biohybrid systems, there have been significant
developments of biohybrids using bacterial swimming power. Unlike
sperm, bacteria occur in multiple areas of the human microbiome[71] making them more viable for variable biomedical
applications. They are also significantly shorter in scale (0.7–7
μm long) compared to other bioactuators allowing them to navigate
in smaller environments. Some of the smallest synthetic cargo delivered
by bacteria include nanoscale liposomes (70 liposomes) bound to MC-1
magnetotactic bacteria (Figure C).[72] Once the biohybrid was incubated
with mammalian cells (J774, NIH/3T3, and Colo205), the immobile cells
could take up the swimming biohybrid with liposomes, exhibiting the
biohybrid’s potential ability as a drug carrying system. For
development of biohybrids with larger cargo loads, bacteria coupled
with nano- or microparticles have been investigated (Figure D,E). Initial work with bacteria–-particle
swimmers attached Serratia marcescens to 10 μm
polystyrene beads and achieved a biohybrid with an average velocity
of 15 μm/s, but with random directionality.[73] A number of methods have been employed to guide bacteria
biohybrid swimming, including chemotaxis,[74,75] pH taxis,[76] and specified cell adhesion
for unified propulsion force.[77] For guided
cell adhesion, directional swimming, and drug delivery, contained
in a single biohybrid, a multifunctional biohybrid was developed.[78] Metal capped (Au, Pt, Fe, Ti) 2 μm and
600 nm polystyrene particles were coupled with Escherichia
coli (E. coli) (Figure D,F). E. coli preferentially
adhered only to the metal cap of the Janus particle without secondary
surface modification[79] or antibodies[80] for simple and rapid biohybrid formation. The
polystyrene side of the Janus particle was modified with the anticancer
agent doxorubicin hydrochloride, demonstrating that the biohybrid
was capable of directed cell adhesion and localized drug attachment.
The preferential adhesion of the bacteria to the metal cap was found
to be related to the hydrophobicity of the metal cap. Such bacteria
biohybrids demonstrate how these systems are moving toward real-world
applicability, but certain obstacles remain. Similar to the sperm
biohybrids, bacteria biohybrids need more experimentation in vivo and sophisticated imaging techniques to achieve
controlled guidance. Materials and architectures, other than particles,
should also be investigated for bacteria biohybrids;[81] this may lead to greater directional guidance and new opportunities
for cargo delivery.
Conclusions
The interest in the
field of artificial micro and nanomotors has
grown steadily over the past decade. This has been both due to the
greater physical understanding that we now have of these systems and
the recent advances in nanotechnology, which let researchers create
and test new designs of these motors. Some of these designs have been
driven purely by our interest in creating biomimetic swimmers at the
microscale such as asymmetric colloidal particles that are gravitactic,
similar to paramecium, or rheotactic, akin to sperm and bacteria.
Colloidal swimmers that sense and respond to each other via chemical
fields were also realized mimicking population scale effects from
the microbial world. Experiments with biomimetic colloidal microswimmers
could enhance our understanding of the physical mechanisms involved
in biological swimmers.The other motivation for the design
of micromotors is more practical,
to develop autonomous microdevices that can perform useful tasks,
either independently or in response to external signals. A number
of applications have been demonstrated with these micromotors ranging
from cargo delivery to environmental remediation and bio sensing.
It is imperative in this case to have a design that is optimized for
particular applications, provides for precise motion control, and
is fully compatible with the system. The compatibility has been a
significant challenge especially when it comes to biological applications,
mostly due to the fuels, which are generally non-biocompatible. However,
recent progress and current efforts to incorporate biological components
such as enzymes and biological swimmers into synthetic micromotors
seems to be addressing this problem in a significant way, opening
up exciting areas of application for artificial micromotors.
Authors: Loai K E A Abdelmohsen; Marlies Nijemeisland; Gajanan M Pawar; Geert-Jan A Janssen; Roeland J M Nolte; Jan C M van Hest; Daniela A Wilson Journal: ACS Nano Date: 2016-01-28 Impact factor: 15.881
Authors: Samuel Sanchez; Alexander A Solovev; Stefan M Harazim; Christoph Deneke; Yong Feng Mei; Oliver G Schmidt Journal: Chem Rec Date: 2011-09-06 Impact factor: 6.771
Authors: Jintao Tong; Dalei Wang; Ye Liu; Xin Lou; Jiwei Jiang; Bin Dong; Renfeng Dong; Mingcheng Yang Journal: Proc Natl Acad Sci U S A Date: 2021-10-19 Impact factor: 11.205
Authors: Jingxin Shao; Mona Abdelghani; Guizhi Shen; Shoupeng Cao; David S Williams; Jan C M van Hest Journal: ACS Nano Date: 2018-05-09 Impact factor: 15.881
Authors: Enrique Contreras; Christian Palacios; I Brian Becerril-Castro; José M Romo-Herrera Journal: Micromachines (Basel) Date: 2021-05-19 Impact factor: 2.891