**5.1 Cargo delivery**

Cargo delivery is one of the most important envisioned applications of micro-/ nanomotors. Relying on the properties of cargoes, tailored methods are desired for their corresponding delivery. A general process of how to synthesize micro-/ nanomotors and employ them to deliver cargo molecules has been shown in **Figure 20** [4].

For the cargo delivery by micro-/nanomotors, the cargo could simply be connected to the motors by magnetic attraction. The delivery of drug-loaded magnetic poly(D,L-lactic-co-glycolic acid) (PLGA) microparticles has been studied by both chemically propelled, as shown in **Figure 21A** [52–54], and magnetically driven micro-/nanomotors. For charged cargoes, electrostatic interaction between cargoes and micro-/nanomotors could be applied for the pick-up process. A common scheme introducing charged portions into micro-/nanomotors is to incorporate a negatively charged polymer part. Sen et al. reported that a PPy part was incorporated to a nanowire via electropolymerization, which could be attached to oppositely charged polystyrene amidine cargo via electrostatic interaction, as shown in **Figure 21A**. A photo-chemically triggered cargo unloading manner was proposed for cargoes loaded nanowires via electrostatic interaction. An additional Ag portion

### **Figure 20.**

*Electrodeposited aptamer-functionalized micro/nanomotors for selective loading, deliver, and unloading of a protein cargo. Copyright 2009, ACS Publications.*

introduces differences in surface and catalytic properties. Hydrazine (N2H4) is another chemical stimulus observed to be effective to accelerate the propulsion of Au/Pt-CNT nanomotors. For bubble-propelled micro-/nanomotors, surfactants are significantly critical to the mobility of motors, resulting from they can stimulate

*Micro/nanomotor's motion controlled by chemical gradient in microfluidic channel. Copyright 2013, Wiley*

*Micro/nanojet's propulsion controlled by temperature. Copyright 2011, ACS Publications. Copyright 2013,*

*Smart Nanosystems for Biomedicine, Optoelectronics and Catalysis*

Solovev et al. reported that the production of large microbubbles from small ensembles of microjets generated a chemophoretic attraction force and a capillary force that pulled other microjets into the swarm. A more complicated experiment was demonstrated by Baraban et al., who reported a controllable manner to study the chemotactic behavior of Janus motors and tubular microjets in microfluidic channels. Both types of motors move toward the gradient of the fuel without the

bubble production and detachment.

**Figure 18.**

**Figure 19.**

**186**

*Online Library.*

*RSC Publications.*

influence of capillary forces, as shown in **Figure 19** [51].

mesoporous SiO2 nanoparticles (MSNs) were fabricated by using a base-catalyzed sol–gel method. Afterwards, MSNs were dispersed on an Si substrate to form a monolayer and subsequently deposited with evaporated Cr (chromium) and Pt. A brief sonication resulted in the Janus MSNs becoming spread in a solution of the anticancer drug doxorubicin hydrochloride to pick up the cargo, and subsequently mixing with 1-mg mL<sup>1</sup> egg phosphatidylcholine containing 1% folic acid resulted

*Catalytic Micro/Nanomotors: Propulsion Mechanisms, Fabrication, Control, and Applications*

The Wang's group reported a great capability of microtubular motors for the selective loading, delivery, and isolation of distinct target analytes of biological relevance. They bio-functionalized the outer walls of microtubes with antibodies, aptamers, lectin receptors, and ss-DNA, and thus the isolation modes of cancer cells, bacteria, proteins, and nucleic acids could be demonstrated in **Figure 21C** [56]. The authors made use of rolled-up microtubes with Au layers for thiol

Campuzano and his colleagues functionalized Au/Ni/PANI/Pt micromotors with concanavalin A (ConA) to enable selective loading of pathogenic bacteria from fuelenhanced real samples, as shown in **Figure 21D** [57]. The loading, transport, and unloading events were observed by optical microscopy. The delivery of pathogenic bacteria by magnetic polymeric drug carriers could represent the basis of an attractive propulsion-based theranostics scheme. In related work, the same group later functionalized artificial catalytic micromotors with antibodies to enable in-chip immunoassays, as shown in **Figure 21E** [58]. Kuralay et al. fabricated poly(3 aminophenylboronic acid) (PAPBA)/Ni/Pt tubular micromotors that selectively recognize monosaccharides, which were capable of loading and drop off of yeast

One of the primary environmental applications of micro-/nanomotors is to adsorb the pollutants in water. Remediation agents could be incorporated with micro-/nanomotors as the outer surface to contribute to the purification process during propulsion. Soler et al. studied the application of microtube motors decorated with a Fe outer surface to degrade organic contaminants in water via the Fenton oxidation, as shown in **Figure 22A** [60]. Wang et al. reported the application of PEDOT/Pt microtubular motors to promote the degradation of chemical threats, as shown in **Figure 22B** [61]. In brief, the oxidation of an organophosphate

micromotors, which resulted in an efficient mixing of the treated aqueous solution

alkanethiols on the Au outer surface could pick up and deliver oil droplets resulting from strong interactions between them, as shown in **Figure 22C** [62]. The same group also incorporated the rough external Au layer of microengines with long chains of self-assembled monolayers to create a super-hydrophobic absorbent layer

The application of micro-/nanomotors as chemical sensors is based on the case that the propulsion speed of micro-/nanomotors can be converted into an analytically useful signal. The interaction of certain compounds in the sample with the

Surface modifications of micro-/nanomotors with a hydrophobic layer could also activate them to load oil droplets. Guix et al. demonstrated that the functionalized

nerve agent by H2O2 was enhanced in the presence of the self-propelled

Au/Ni/PEDOT/Pt microtubes with a self-assembled monolayer (SAM) of

without the aid of external mechanical stirrers.

for oil loading, as shown in **Figure 22D** [62].

**5.3 Chemical sensors**

**189**

modification and template-assisted microjets with polymer walls.

in encapsulation.

*DOI: http://dx.doi.org/10.5772/intechopen.90456*

cells, as shown in **Figure 21F** [59].

**5.2 Environmental remediation**

#### **Figure 21.**

*(A) Examples of the delivery of cargo using solid micro/nanorods: (a) cargo pick-up, (b) cargo delivery, and (c) cargo release, respectively. (B) Synthesis procedures for Janus spherical micro/nanomotors, drug picking-up, lipid bilayer functionalization, and drug unloading (DOX = doxorubicin hydrochloride). (C) Selective binding and delivery of biological analytes and cells by functionalized microjets. (D) Direct optical visualization of pickup, transportation, and delivery of E. coli bacteria and polymeric drug-carrier spheres. (E) In-chip immunoassays for in situ picking up and delivery of target proteins. (F) Selective recognition of monosaccharides for loading and unloading of yeast cells. Copyright 2008, ACS Publications. Copyright 2010, Wiley Online Library. Copyright 2010, Wiley Online Library. Copyright 2014, Wiley Online Library. Copyright 2011, RSC Publications. Copyright 2012, ACS Publications. Copyright 2013, RSC Publications. Copyright 2012, ACS Publications.*

in a nanowire will be dissolved rapidly in the presence of H2O2, chloride ions (Cl), and ultraviolet (UV) light, resulting in releasing of the cargo.

Garcia-Gradilla and colleagues demonstrated that the incorporation of a negatively charged polypyrrole polystyrene sulfonate (PPyPSS) portion with an ultrasound-propelled nanowire could be served as a pH-sensitive carrier for positively charged drugs via electrostatic interaction. The unloading of the drugs was theoretically realized by a protonated PPyPSS portion in an acidic environment. The same group also reported drug-loaded nanowires depending on a nanoporous Au portion with a large surface area. Such a nanoporous device is synthesized by dealloying the Ag portion of an Au/Ag alloy grown by the coelectrodeposition of Au and Ag. The picking up of the drug doxorubicin in the nanopores via electrostatic interactions with the polymeric coating of the nanowire motors and NIR lightstimulated drop off were reported as well.

Xuan et al. reported the fabrication of self-propelled Janus nanomotors in a diameter of 75 nm. The steps are illustrated in **Figure 21B** [55]. Spherical

*Catalytic Micro/Nanomotors: Propulsion Mechanisms, Fabrication, Control, and Applications DOI: http://dx.doi.org/10.5772/intechopen.90456*

mesoporous SiO2 nanoparticles (MSNs) were fabricated by using a base-catalyzed sol–gel method. Afterwards, MSNs were dispersed on an Si substrate to form a monolayer and subsequently deposited with evaporated Cr (chromium) and Pt. A brief sonication resulted in the Janus MSNs becoming spread in a solution of the anticancer drug doxorubicin hydrochloride to pick up the cargo, and subsequently mixing with 1-mg mL<sup>1</sup> egg phosphatidylcholine containing 1% folic acid resulted in encapsulation.

The Wang's group reported a great capability of microtubular motors for the selective loading, delivery, and isolation of distinct target analytes of biological relevance. They bio-functionalized the outer walls of microtubes with antibodies, aptamers, lectin receptors, and ss-DNA, and thus the isolation modes of cancer cells, bacteria, proteins, and nucleic acids could be demonstrated in **Figure 21C** [56]. The authors made use of rolled-up microtubes with Au layers for thiol modification and template-assisted microjets with polymer walls.

Campuzano and his colleagues functionalized Au/Ni/PANI/Pt micromotors with concanavalin A (ConA) to enable selective loading of pathogenic bacteria from fuelenhanced real samples, as shown in **Figure 21D** [57]. The loading, transport, and unloading events were observed by optical microscopy. The delivery of pathogenic bacteria by magnetic polymeric drug carriers could represent the basis of an attractive propulsion-based theranostics scheme. In related work, the same group later functionalized artificial catalytic micromotors with antibodies to enable in-chip immunoassays, as shown in **Figure 21E** [58]. Kuralay et al. fabricated poly(3 aminophenylboronic acid) (PAPBA)/Ni/Pt tubular micromotors that selectively recognize monosaccharides, which were capable of loading and drop off of yeast cells, as shown in **Figure 21F** [59].

#### **5.2 Environmental remediation**

One of the primary environmental applications of micro-/nanomotors is to adsorb the pollutants in water. Remediation agents could be incorporated with micro-/nanomotors as the outer surface to contribute to the purification process during propulsion. Soler et al. studied the application of microtube motors decorated with a Fe outer surface to degrade organic contaminants in water via the Fenton oxidation, as shown in **Figure 22A** [60]. Wang et al. reported the application of PEDOT/Pt microtubular motors to promote the degradation of chemical threats, as shown in **Figure 22B** [61]. In brief, the oxidation of an organophosphate nerve agent by H2O2 was enhanced in the presence of the self-propelled micromotors, which resulted in an efficient mixing of the treated aqueous solution without the aid of external mechanical stirrers.

Surface modifications of micro-/nanomotors with a hydrophobic layer could also activate them to load oil droplets. Guix et al. demonstrated that the functionalized Au/Ni/PEDOT/Pt microtubes with a self-assembled monolayer (SAM) of alkanethiols on the Au outer surface could pick up and deliver oil droplets resulting from strong interactions between them, as shown in **Figure 22C** [62]. The same group also incorporated the rough external Au layer of microengines with long chains of self-assembled monolayers to create a super-hydrophobic absorbent layer for oil loading, as shown in **Figure 22D** [62].

#### **5.3 Chemical sensors**

The application of micro-/nanomotors as chemical sensors is based on the case that the propulsion speed of micro-/nanomotors can be converted into an analytically useful signal. The interaction of certain compounds in the sample with the

in a nanowire will be dissolved rapidly in the presence of H2O2, chloride ions (Cl),

*(A) Examples of the delivery of cargo using solid micro/nanorods: (a) cargo pick-up, (b) cargo delivery, and (c) cargo release, respectively. (B) Synthesis procedures for Janus spherical micro/nanomotors, drug picking-up, lipid bilayer functionalization, and drug unloading (DOX = doxorubicin hydrochloride). (C) Selective binding and delivery of biological analytes and cells by functionalized microjets. (D) Direct optical visualization of pickup, transportation, and delivery of E. coli bacteria and polymeric drug-carrier spheres. (E) In-chip immunoassays for in situ picking up and delivery of target proteins. (F) Selective recognition of monosaccharides for loading and unloading of yeast cells. Copyright 2008, ACS Publications. Copyright 2010, Wiley Online Library. Copyright 2010, Wiley Online Library. Copyright 2014, Wiley Online Library. Copyright 2011, RSC Publications. Copyright 2012, ACS Publications. Copyright 2013, RSC Publications. Copyright 2012, ACS Publications.*

Garcia-Gradilla and colleagues demonstrated that the incorporation of a nega-

Xuan et al. reported the fabrication of self-propelled Janus nanomotors in a

diameter of 75 nm. The steps are illustrated in **Figure 21B** [55]. Spherical

tively charged polypyrrole polystyrene sulfonate (PPyPSS) portion with an ultrasound-propelled nanowire could be served as a pH-sensitive carrier for positively charged drugs via electrostatic interaction. The unloading of the drugs was theoretically realized by a protonated PPyPSS portion in an acidic environment. The same group also reported drug-loaded nanowires depending on a nanoporous Au portion with a large surface area. Such a nanoporous device is synthesized by dealloying the Ag portion of an Au/Ag alloy grown by the coelectrodeposition of Au and Ag. The picking up of the drug doxorubicin in the nanopores via electrostatic interactions with the polymeric coating of the nanowire motors and NIR light-

and ultraviolet (UV) light, resulting in releasing of the cargo.

*Smart Nanosystems for Biomedicine, Optoelectronics and Catalysis*

stimulated drop off were reported as well.

**Figure 21.**

**188**

#### **Figure 22.**

*(A) Organic pollutants degraded by multifunctional Fe/Pt micromotors in H2O2 solutions. (B) Accelerated oxidation of organophospate nerve agents by using micromotors as active mixers. (C) Loading of oil droplets by alkanethiol-modified microtubes. (D) Picking up and loading of oil, enabled by a superhydrophobic-modified outer layer. Copyright 2013, ACS Publications. Copyright 2013, Wiley Online Library. Copyright 2012, ACS Publications.*

catalytic sites of micro-/nanomotors leads to the alteration of their propulsion speed and is related to the concentration of an analyte in solution, as shown in **Figure 23** [63–66]. Although the field is still in its infancy, micro-/nanomotors as chemical sensors could have a number of advantages over conventional either optical or electrochemical sensors, such as sensitivity, selectivity, immunity to electrical interferences, operation in a wireless manner, and only requiring a minute amount of sample. In the past few years, some research groups demonstrated the ability of micro-/nanomotors to detect inorganic electrolytes present in blood, heavy metals, organic compounds such as dimethyl sulfoxide (**Figure 23A**) [63], uric acid, blood proteins such as bovine serum albumin (BSA), glucose oxidase enzymes and g-globulin, amino acids containing thiol groups, for instance, methionine, cysteine, and serine (**Figure 23D**) [65], peptides such as glutathione, and DNA (**Figure 23A**).

addition, the aforementioned vortex effect generated by the propulsion of micromotors can boost the mass transfer of the target toward the functionalized microjet surface (i.e. "on-the-fly") as well as assist the mass transfer of the target molecule within the matrix of a sample solution toward a sensing surface, where the bio-receptor is situated and the target is expected to be selectively attached, as

*(A) Detection of Ag-tagged nucleic acid, which alters the propulsion of the micro-/nanomotors. (B) Antibodydecorated micromotor for protein detection. (C) Micromotor-based multiplexed immunoassay via different microscopic tracers. (D) Effect of the concentration of DMSO (dimethyl sulfoxide), cysteine, and serine on the swimming speeds of the microtubular motors. (E) Microarray immunoassay assisted by microengines. Copyright 2013, ACS Publications. Copyright 2012, ACS Publications. Copyright 2014, RSC Publications. Copyright*

*Catalytic Micro/Nanomotors: Propulsion Mechanisms, Fabrication, Control, and Applications*

*DOI: http://dx.doi.org/10.5772/intechopen.90456*

The pioneering micro-/nanomotors offer considerable promise for biomedical

Micro-/nanojets have proven to be capable of drilling into biomaterials and soft tissues. Rolled-up thin nanomembranes can asymmetrically result in sharp edges being engineered. Nanojets were self-propelled and externally directed toward immobilized cancer cells and embedded in their interior, as shown in **Figure 25A** [68]. However, the toxicity of the H2O2 fuel used for the movement leads to the cells undergoing apoptosis after short periods. Therefore, other environmentally

applications, as shown in **Figure 24** [67]. Herein, we outline some important

advances of micro-/nanomotors in the biomedical field.

*2013, RSC Publications. Copyright 2014, Wiley Online Library.*

shown in **Figure 23E** [66].

**Figure 23.**

**191**

**5.4 Biomedical applications**

García and his colleagues demonstrated the first antibody-loaded tubular microengines, which were developed to load and deliver target molecules between different microfluidic chambers. Catalytic polymer/Ni/Pt microengines were biofunctionalized with antibodies targeting Immunoglobulin G (IgG) protein molecule, as a model protein, in order to realize a micromotor-based immunoassay providing "on-the-fly" loading and isolation/sorting capabilities, as shown in **Figure 23B** [57]. The immunocomplex could be simply observed by optical microscope through using an antigen/antibody labeled with a polymeric sphere tracer. This innovative work is highly selective and excludes time-consuming washing steps, accelerating and simplifying the general immunoassay procedures. Taking advantage of these features, Yu et al. employed antibody-loaded AuNP/PANI/Pt micromotors to exhibit rapid "on-the-fly" sandwich immunocomplexes targeting carcinoembryonic antigen. The operation takes 5 minutes with a measuring threshold of 1–1000 ng mL<sup>1</sup> . In addition, labeling the loaded proteins with microscopic particles demonstrating different sizes and shapes facilitates the multiplexed analysis of proteins, as proved by Vilela and his colleagues (**Figure 23C**) [64]. In

*Catalytic Micro/Nanomotors: Propulsion Mechanisms, Fabrication, Control, and Applications DOI: http://dx.doi.org/10.5772/intechopen.90456*

#### **Figure 23.**

catalytic sites of micro-/nanomotors leads to the alteration of their propulsion speed and is related to the concentration of an analyte in solution, as shown in **Figure 23** [63–66]. Although the field is still in its infancy, micro-/nanomotors as chemical sensors could have a number of advantages over conventional either optical or electrochemical sensors, such as sensitivity, selectivity, immunity to electrical interferences, operation in a wireless manner, and only requiring a minute amount of sample. In the past few years, some research groups demonstrated the ability of micro-/nanomotors to detect inorganic electrolytes present in blood, heavy metals, organic compounds such as dimethyl sulfoxide (**Figure 23A**) [63], uric acid, blood proteins such as bovine serum albumin (BSA), glucose oxidase enzymes and g-globulin, amino acids containing thiol groups, for instance, methionine, cysteine, and serine (**Figure 23D**) [65], peptides such as glutathione, and DNA (**Figure 23A**). García and his colleagues demonstrated the first antibody-loaded tubular microengines, which were developed to load and deliver target molecules between different microfluidic chambers. Catalytic polymer/Ni/Pt microengines were biofunctionalized with antibodies targeting Immunoglobulin G (IgG) protein molecule, as a model protein, in order to realize a micromotor-based immunoassay providing "on-the-fly" loading and isolation/sorting capabilities, as shown in **Figure 23B** [57]. The immunocomplex could be simply observed by optical microscope through using an antigen/antibody labeled with a polymeric sphere tracer. This innovative work is highly selective and excludes time-consuming washing steps, accelerating and simplifying the general immunoassay procedures. Taking advantage of these features, Yu et al. employed antibody-loaded AuNP/PANI/Pt micromotors to exhibit rapid "on-the-fly" sandwich immunocomplexes targeting carcinoembryonic antigen. The operation takes 5 minutes with a measuring thresh-

*(A) Organic pollutants degraded by multifunctional Fe/Pt micromotors in H2O2 solutions. (B) Accelerated oxidation of organophospate nerve agents by using micromotors as active mixers. (C) Loading of oil droplets by alkanethiol-modified microtubes. (D) Picking up and loading of oil, enabled by a superhydrophobic-modified outer layer. Copyright 2013, ACS Publications. Copyright 2013, Wiley Online Library. Copyright 2012, ACS*

*Smart Nanosystems for Biomedicine, Optoelectronics and Catalysis*

. In addition, labeling the loaded proteins with microscopic

particles demonstrating different sizes and shapes facilitates the multiplexed analy-

sis of proteins, as proved by Vilela and his colleagues (**Figure 23C**) [64]. In

old of 1–1000 ng mL<sup>1</sup>

**190**

**Figure 22.**

*Publications.*

*(A) Detection of Ag-tagged nucleic acid, which alters the propulsion of the micro-/nanomotors. (B) Antibodydecorated micromotor for protein detection. (C) Micromotor-based multiplexed immunoassay via different microscopic tracers. (D) Effect of the concentration of DMSO (dimethyl sulfoxide), cysteine, and serine on the swimming speeds of the microtubular motors. (E) Microarray immunoassay assisted by microengines. Copyright 2013, ACS Publications. Copyright 2012, ACS Publications. Copyright 2014, RSC Publications. Copyright 2013, RSC Publications. Copyright 2014, Wiley Online Library.*

addition, the aforementioned vortex effect generated by the propulsion of micromotors can boost the mass transfer of the target toward the functionalized microjet surface (i.e. "on-the-fly") as well as assist the mass transfer of the target molecule within the matrix of a sample solution toward a sensing surface, where the bio-receptor is situated and the target is expected to be selectively attached, as shown in **Figure 23E** [66].

### **5.4 Biomedical applications**

The pioneering micro-/nanomotors offer considerable promise for biomedical applications, as shown in **Figure 24** [67]. Herein, we outline some important advances of micro-/nanomotors in the biomedical field.

Micro-/nanojets have proven to be capable of drilling into biomaterials and soft tissues. Rolled-up thin nanomembranes can asymmetrically result in sharp edges being engineered. Nanojets were self-propelled and externally directed toward immobilized cancer cells and embedded in their interior, as shown in **Figure 25A** [68]. However, the toxicity of the H2O2 fuel used for the movement leads to the cells undergoing apoptosis after short periods. Therefore, other environmentally

**Figure 25C** [69]. Ultrasonic waves can also generate the propulsion of micro-/ nanomotors, as shown in **Figure 25D** and **E**) [70, 71]. Bio-functionalized nanowires propelled by ultrasound have been applied for bio-sensing, and the first results of magnetic steering toward cells have been studied. Mallouk et al. demonstrated the

*Catalytic Micro/Nanomotors: Propulsion Mechanisms, Fabrication, Control, and Applications*

In this chapter, the previously reported Pt-based micro-/nanomotors are presented. In detail, the propulsion mechanisms, fabrication methods, propulsion controlling methods, and applications of these synthetic micro-/nanomotors developed in the past years are summarized accordingly. Despite the rapid and significant advances in micro-/nanomotors, challenges such as specifically practical applications and smart controlling still remain to be resolved. In addition, advanced

This work was supported by Ministry of Education, Singapore, under "MOE

structure design and fabrication methods are demanded.

There are no conflicts of interest to declare.

internalization of a nanowire-based motor inside living cells, as shown in **Figure 25D**. Developing biocompatible materials and fuels for artificial micro-/ nanomotors or the use of noninvasive external triggered motors may pave the way for biomedical applications of micro-/nanomotors in the near future [72–80].

**6. Conclusions**

**Acknowledgements**

**Conflicts of interest**

**193**

2011-T2-2-156, ARC 18/12" program.

*DOI: http://dx.doi.org/10.5772/intechopen.90456*
