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Micro- and nanorobots based sensing and biosensing
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Review Article Micro- and nanorobots based sensing and biosensing Lei Kong 1,3 , Jianguo Guan 3,∗ and Martin Pumera 1,2,∗ Synthetic micro- and nanorobots have attracted considerable attentions for their potential applications in environment, biomedicine and microengineering. In this review, we summarize the recent works on micro/nanorobots based sensing and biosensing according to different mechanisms: motion based sensing, electrochemical sensing with micro/nanorobots and fluorescent, electrochemiluminescent, colorimetric sensing with micro/nanorobots. Micro/nanorobots offer a convenient and active detection for nucleic acid, protein, glucose, heavy metal ions, etc. in solution and surrounding atmosphere. Furthermore, the detection sensitivity and efficiency has been significantly improved due to the stirring in solution by the motion of micro/nanorobots. Addresses 1 Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore 2 Center for the Advanced Functional Nanorobots, Department of Inorganic Chemistry, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague 6, Czech Republic 3 State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan 430070, People’s Republic of China ∗
Corresponding authors: Guan, Jianguo ([email protected]), Pumera, Martin ([email protected], [email protected])
Current Opinion in Electrochemistry 2018, 10:174–182 This review comes from a themed issue on Sensors and Biosensors
particular, due to the excellent movement, micro/nanorobots can attach to the target molecules actively and enhance the mass transfer in solution [28–32], which offers unrivaled merits in sensing and biosensing [33–40]. Herein, this article reviews the recent works on sensing and biosensing with micro/nanorobots, which can be divided into three categories according to different sensing mechanisms (Scheme 1): (1) Chemical sensing based on micro/nanorobots motion. Any changes in catalysts activity or fuels will lead to different velocities of micro/nanorobots, which can be observed for chemicals detection in solution or surrounding atmosphere; (2) Electrochemical sensing with micro/nanorobots. The chemicals in solution can be detected by electrochemical method and the detection sensitivity is enhanced due to the stirring by the motion of micro/nanorobots. Moreover, the motion of micro/nanorobots can be monitored by electrochemical changes on the electrode; (3) Fluorescent, electrochemiluminescent (ECL) and colorimetric sensing with micro/nanorobots. The motion of micro/nanorobots provides the quick detection for the change of fluorescence, electrochemiluminescence and color signals caused by the targets molecules, which is sensitive and visualized. In general, micro/nanorobots offer a convenient and active detection for nucleic acid, protein, glucose, heavy metal ions, and so on. Furthermore, the detection sensitivity and efficiency can also be improved due to the stirring and enhanced mass transfer in solution by the motion.
˘ Edited by Robert Sandulescu and Cecilia Cristea For a complete overview see the Issue and the Editorial Available online 28 June 2018 https://doi.org/10.1016/j.coelec.2018.06.004 2451-9103/© 2018 Elsevier B.V. All rights reserved.
Introduction Synthetic micro- and nanorobots can convert the energy from environment into autonomous movement, which have attracted significant attentions during last decades [1–11]. Various materials and structures were utilized to build micro/nanorobots that exhibited potential applications in environmental detection and remediation [12–18], biomedicine and microengineering [19–27]. In Current Opinion in Electrochemistry 2018, 10:174–182
Chemical sensing based on micro/nanorobots motion Catalysts and fuels are the two essential elements of catalytic micro/nanorobots [47]. Any changes in catalysts activity or fuels will lead to different velocities of micro/nanorobots, which can be observed for chemicals detection in solution. The trace silver detection with catalytic nanomotors was firstly reported by Wang and coworkers (Figure 1A) [41●● ]. According to their previous work [48], the nanowires motors will speed up by using Ag/Au alloy to replace Au segment because of the larger potential difference between Ag/Au and Pt. Thus, the Au–Pt nanomotors can speed up in H2 O2 solution with trace Ag+ present due to the deposition of silver on nanomotors. Moreover, the speed of nanomotors will decrease in solutions containing K+ , Pd2+ , Ni2+ , etc. owing to the increment of solution conductivity. Accordingly, the Au–Pt nanomotors have capacity to detect trace Ag+ in solution by observing the motion with www.sciencedirect.com
Micro- and nanorobots based sensing and biosensing Kong, Guan and Pumera
Scheme 1
Different sensing mechanisms with micro/nanorobots.
optical microscope. Subsequently, they developed the motion-based nucleic acid detection assay, which relied on the duplex formation of nucleic acid target with thiolated Au–Pt nanomotors and silver nanoparticle tagged detector probe (Figure 1B) [42● ]. The dissolution of combined Ag nanoparticles in H2 O2 fuel will release Ag+ , which speed up the Au–Pt nanomotors. Furthermore, the velocity of Au–Pt nanomotors relates to the number of captured Ag nanoparticles, which can be adjusted by the concentration of nucleic acid targets. Finally, the resulting distance signals provided convenient measurements of nucleic acid targets at attomole level. Later, Van Nguyen and Minteer presented a new strategy for micro/nanorobots-based DNA detection [49]. The motion-based signal was produced through the attachment of DNA target modified Pt nanoparticles via specific DNA hybridization on tubular micromotors. Similarly, the micromotor-based multiplexed immunoassay for selective detection of proteins were performed by tagging the analytes with microparticles of different sizes and shapes, which helped to visualize the antibody-protein recognition [50]. At the same time, Yu et al. fabricated antibody modified micromotors for cancer biomarkers detection through selective recognition according to the decrease of velocity [51]. It is well-known that some chemicals in solution like heavy metals ions or organics may poison the catalysts [52,53], which leads to the decrease of velocity and limited lifetime of micro/nanorobots. Orozco et al. prepared catalase powered “microfish” for water testing (Figure 1C) [43]. The changes in swimming performance and lifetime of artificial microswimmers were evaluated for
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testing the toxin in water due to their inhibition to the catalase activity. Recently, Sánchez and coworkers fabricated a microcapsule motor powered by biocatalytic decomposition of urea. Ag+ or Hg2+ could be the inhibitors for affecting the enzymatic activity of urease, which enables the motors to serve as an active sensor for heavy metals [54]. Besides the enzyme-powered micromotors, Pumera and coworkers demonstrated that small molecules containing sulphur could poison Pt-catalyst micromotors because of hydroxyl radicals quenching and O2 bubbles reducing, which provides potential application of Pt-catalyst micromotors for detecting cysteine, methionine and glutathione (Figure 1D) [44]. Then, they found that Pt-based microrobots could sense the presence of Pb2+ selectively in solution [55● ]. Specifically, Pb2+ and Cd2+ can decrease the activity of Pt by attaching on the surface and covering the active sites. In addition, due to the attachment and attached area of Pb2+ is stronger and larger than that of Cd2+ , the velocity and active number of Pt-based microrobots will decrease more obviously in Pb2+ solution with low concentration. Motion-based pH sensor relies on the velocity change with variation of pH values. Guix and coworkers reported that carbonate-based Janus micromotors could move in ultra-light acidic environment (pH 6.5) generated by HeLa cells, which shows the potential ability to sense extremely light acidic environments [56● ]. Later, Su et al. developed a cartridge-case-like micromotor that consists of a gelatin shell with Pt nanoparticles decorated on inner surface. Interestingly, the wall thickness and size of opening will change with different pH values in solution, which has impact on the activity of Pt nanoparticles for decomposition of H2 O2 and bubble generation frequency from the micromotor. Finally, the velocity of micromotors will increase with increment of pH value in solution from 0 to 14 (Figure 1E), which made it possible to be a pH sensor [45]. In general, the variation of fuels will lead to the change of velocity [57,58], which can be interpreted as the output signals for fuel molecules detection. Gao et al. synthesized Ir/SiO2 Janus micromotors which could be powered at remarkably low concentration of hydrazine (0.0000001%), exhibiting the possibility to detect N2 H4 in solution by motion [59● ]. According to above study, Dong and coworkers developed the remotely triggered catalytic Ir– Au micromotors that were responsive to hydrazine vapor from the surrounding atmosphere into running solution (Figure 1F), exhibiting the capability to act as highly selective sensors for toxic gases [46]. Similarly, the enzyme substrates such as glucose, could be detected by enzymepowered mciromotors owing to the enhanced diffusivity [60,61].
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Figure 1
(A) Ag+ detection based on the motion of Au–Pt nanomotors. Reprinted with permission from ref. [41]. Copyright 2009, American Chemical Society. (B) Schematic of motion-based nucleic acid detection with Au–Pt nanomotors. Reprinted with permission from ref. [42]. Copyright 2010, Springer Nature. (C) Scheme of toxicity testing in water with catalase modified microfish. Reprinted with permission from ref. [43]. Copyright 2013, American Chemical Society. (D) Schematic demonstration of chemical sensing by poisoning Pt-catalyst microjets. Reproduced from ref. [44] with permission from the Royal Society of Chemistry. (E) pH sensing based on cartridge-case-like micromotors. Reprinted with permission from ref. [45]. Copyright 2016, American Chemical Society. (F) Gas sensing with catalytic micromotors powered by a remote fuel source [46].
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Figure 2
(A) Schematic of the Mg/Au Janus micromotors-based strategy for the simultaneous degradation/detection of DPP. Reprinted with permission from ref. [62]. Copyright 2016, American Chemical Society. (B) Scheme of electrochemical setup of the capsule track for monitoring motion. Reprinted with permission from ref. [63●● ]. Copyright 2014, American Chemical Society. (C) Schematic of a micromotor impacting a carbon microfiber electrode surface and the corresponding electrochemical signal generated. Reprinted with permission from ref. [64]. Copyright 2016, American Chemical Society.
Electrochemical sensing with micro/nanorobots Electrochemical sensing relies on the redox reaction change on the electrode or on the disturbance of the double-layer, which provides a low-cost, portable and sensitive detection method [34,65]. Meanwhile, synthetic micro/nanorobots have exhibited the ability to improve the degradation efficiency and detection sensitivity through micromixing and enhanced mass transfer by the motion [66–68]. Cinti and coworkers showed the degradation of nerve agent paraoxon with Au–Ni–Mg Janus micromotors and detection of the by-product p-nitrophenol through electrochemical detection at printable sensor strips [69●● ]. The Au–Ni–Mg Janus micromotors in 0.1 M KCl solution leads to the increment of pH, which decomposes paraoxon into p-nitrophenol. In addition, the detection sensitivity has been increased due to the stirring in solution by the motion of micromotors. Later, Escarpa and coworkers exhibited the same concept of Mg/Au Janus micromotors assisted degradation/detection of diphenyl phthalate (DPP) on disposable screen-printed electrodes (Figure 2A) [62]. More recently, they demonstrated the selective “on-the-fly” detection of D or L-amino acids with D or L-amino acid oxidase-based motors through electrochemical method [70]. The efficient movement of motors leads to the accelerated enzymatic reaction processes without the need of external stirring. Electrochemical measurement is highly sensitive that any disturbance near the electrodes can be read out as current change. Once the motor crossed the working elecwww.sciencedirect.com
trode, there was a disturbance of the electrical doublelayer and rapid increase in cathodic current (Figure 2B) [63●● ]. Therefore, the velocity of motors could be measured and the position of roadblock could be detected according to the electrochemical profiles. Later, the same group tried to monitor the motion of Janus silver micromotors and tubular Cu/Pt micromotors in the same way [64]. The catalytic micromotors passed the electrode and this will lead to the spike on chronoamperogram (Figure 2C). Additionally, the number of spikes on chronoamperogram relates to the number of active micromotors, which can be adjusted by the concentration of H2 O2 fuel. Recently, they monitored the motion of tubular micromotors over the detection electrode in the microfluidic channel [71]. The electrochemical feedback could reflect the motion of micromotors in real-time.
Fluorescent, electrochemiluminescent and colorimetric sensing with micro/nanorobots Fluorescent sensing offers high sensitivity, low-cost and operational simplicity [78]. Merkoçi and coworkers demonstrated the microarray-based immunosensing with micromotors (Figure 3A) [72● ]. The self-propelled micromotors can assist the binding between the immobilized molecular bioreceptor and target molecules in solution due to the mixing by the motion. The bound targets were revealed by the detection of antibodies labeled with fluorophore, which was measured by fluorescence intensity. Furthermore, the molecularly imprinted polymer-based catalytic micromotors for capturing and transporting proteins through selective bonding can also detect proteins Current Opinion in Electrochemistry 2018, 10:174–182
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Figure 3
(A) Microarray-based immunosensing assisted with micromotors. Reprinted with permission from ref. [72● ]. Copyright 2014, Wiley-VCH. (B) Schemes of fabrication and gas sensing of the catalase and FITC decorated PCL-SH single crystal. Reproduced with permission from ref. [73]. Copyright 2016, Royal Society of Chemistry. (C) Intracellular detection of miRNAs by US-propelled ssDNA@GO-functionalized gold nanomotors. Reprinted with permission from ref. [74●● ]. Copyright 2015, American Chemical Society. (D) Schematic of the QD-based microrockets and their ‘‘on-the-fly’’ selective detection of mercury ions based on fluorescence quenching. Reproduced with permission from ref. [75● ]. Copyright 2015, Royal Society of Chemistry. (E) Illustration of enzyme-driven ECL observed on a bipolar swimmer. Reproduced with permission from ref. [76● ]. Copyright 2014, Royal Society of Chemistry. (F) Scheme of self-propelled enzyme-based motor for hydrogen peroxide detection. Reprinted with permission from ref. [77]. Copyright 2015, American Chemical Society.
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with high efficiency in the presence of fluorescent tags [79]. Liu et al. fabricated an all-polymer micromotor that consists of biodegradation polycaprolactone single crystal and catalase, which can move in H2 O2 solution. The micromotors can detect HCl and NH3 gases after modified with fluorescein isothiocyanate (FITC) because the fluorescence intensity varies in response to different pH (Figure 3B) [73]. Fluorescence quenching methods are effective for sensitive detection based on fluorescent turn-off [80]. Wang and coworkers demonstrated the real-time intracellular biosensing of miRNA with ultrasound-propelled nanomotors (Figure 3C) [74●● ]. First, the graphene-oxide (GO) coated gold nanowires were modified with dyelabeled single-stranded DNA (ssDNA) and fluorescence signal was quenched due to the π –π interaction between GO and dye-labeled ssDNA. After the nanowires powered by ultrasound and penetrated the cancer cells, the fluorescence was recovered due to the release of dyelabeled ssDNA from the nanomotor surface through the hybridization with target miRNA. In the same way, they used the fluorophore fluoresceinamine-coated micromotors to detect nerve agents sarin and soman simulants based on fluorescent on-off [81]. The quantum dots with fluorescent property were used to detect the pollutants or toxins in solution through fluorescence quenching. Jurado-Sánchez et al. incorporated CdTe quantum dots into PEDOT/Pt tubular micromotors that exhibited “on-the-fly” Hg2+ detection (Figure 3D) [75● ]. Due to the strong affinity of Hg2+ with COOH-capped QDs and lower solubility of HgTe than CdTe, the electrons preferentially transferred from QDs to Hg2+ and alloyed Cdx Hg1-x Te was formed, which leads to the fluorescence quenching of CdTe QDs. Furthermore, the moving sensor has ability to detect Hg2+ selectively due to the slight fluorescence quenching by Cu2+ and Pb2+ ions. Very recently, they demonstrated magnetocatalytic hybrid Janus micromotors encapsulating phenylboronic acid modified graphene quantum dots for the detection of deadly bacteria endotoxins through fluorescence quenching [82]. Since Sentic and coworkers demonstrated the microswimmers propelled by bipolar electrochemistry and exhibited electrogenerated chemiluminescence (ECL) [83,84], it has attracted considerable attentions for the potential application on sensing and biosensing. Subsequently, they showed the ECL-microswimmers to monitor the glucose concentration in PBS solution (Figure 3E) [76● ]. The glucose in solution can be oxidized by glucose dehydrogenase with the conversion of NAD+ to NADH which promotes Ru(bpy)3 2+ ECL according to the classic co-reactant pathway. In addition, the ECL intensity will change with the concentration of glucose and no ECL signal appeared in the absence of glucose. www.sciencedirect.com
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Escarpa and coworkers exhibited the visual detection of H2 O2 with HRP enzyme and SDS surfactant released motor (Figure 3F) [77]. The cone shapes of the pipet tips containing SDS and HRP are propelled by the Marangoni effect. Additionally, the released HRP with H2 O2 present will oxidize TMBRED to TMBOX with blue color, which provides the method for visual detection of H2 O2 . Very recently, Wang and coworkers showed the naked-eye immunoassay of cortisol with micromotors [85]. The combination of cortisol-HRP with anti-cortisol functionalized micromotors in TMB/H2 O2 solution leads to the production of deep blue TMB that can be seen with naked eyes. In addition, the detection response and sensitivity was greatly increased by the motion of micromotors.
Conclusions and perspectives In this review, we have concluded the recent works on micro/nanorobots-based sensing and biosensing according to the mechanisms. (1) Chemical sensing based on micro/nanorobots motion. The chemicals in solution or surrounding atmosphere can be detected by the variation of micro/nanorobots velocity with microscope due to the impacts on catalysts or fuels; (2) Electrochemical sensing with micro/nanorobots. The chemicals in solution and the motion of micro/nanorobots can be detected and monitored by electrochemical changes on the electrode in real-time; (3) Fluorescent, ECL and colorimetric sensing with micro/nanorobots. The motion of micro/nanorobots offers the quick and visualized detection on the change of fluorescence, electrochemiluminescence and color signals caused by the target molecules. In general, micro/nanorobots offer an “on-the-fly” sensing and biosensing platform due to the stirring and enhanced mass transfer by the motion. Additionally, their small size and highly controlled movement make it possible to work precisely in microfluidic chips or blood vessels and in solution with microliters, which can improve the sensing and biosensing in microenvironment that the current sensing technology cannot achieve. However, there still are some issues to be solved. (1) The motion-based sensing relies on the change of velocity calculated from several motors under the observation of microscope. Accordingly, a direct method should be developed for on site interpretation. (2) Chemically powered micro/nanorobots which produce bubbles lead to the disturbance near the electrode and need additional fuels, which may bring interferences to the assay. Thus, fuel-free micro/nanorobotsbased sensing should be more appropriate. (3) The fabrication of micro/nanorobots should be uniform, which makes the motion more stable and the detection results more standard and repeatable. (4) In order to compare against other biosensing strategies, the detection sensitivity and accuracy should be further improved for the commercialization in the future. Currently, micro/nanorobots have advantages in microenvironmental sensing. Current Opinion in Electrochemistry 2018, 10:174–182
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Conflict of interest The authors declare no competing financial interest.
18. Parmar J, Villa K, Vilela D, Sánchez S: Platinum-free cobalt ferrite based micromotors for antibiotic removal. Appl Mater Today 2017, 9:605–611.
Acknowledgments
19. Wang J, Gao W: Nano/microscale motors: biomedical opportunities and challenges. ACS Nano 2012, 6:5745–5751.
Authors acknowledge A∗ Star grant SERC A1783c0005 (Singapore) and the National Natural Science Foundation of China (21474078 and 51521001). L. K. acknowledges the Scholarship Fund from China Scholarship Council (CSC No. 201606950043). This work was supported by the project Advanced Functional Nanorobots (reg. No. CZ.02.1.01/0.0/0.0/15_003/0000444 financed by the EFRR) by Czech Republic.
References and recommended reading Papers of particular interest, published within the period of review, have been highlighted as: •
Paper of special interest. Paper of outstanding interest.
••
1.
Paxton WF, Sundararajan S, Mallouk TE, Sen A: Chemical locomotion. Angew Chem Int Ed Engl 2006, 45:5420–5429.
2.
Sengupta S, Ibele ME, Sen A: Fantastic voyage: designing self-powered nanorobots. Angew Chem Int Ed Engl 2012, 51:8434–8445.
3. Guix M, Mayorga-Martinez CC, Merkoci A: Nano/micromotors in ●● (bio)chemical science applications. Chem Rev 2014, 114:6285–6322. All motion mechanisms of nano/micromotors are discussed. 4.
Dey KK, Sen A: Chemically propelled molecules and machines. J Am Chem Soc 2017, 139:7666–7676.
5.
Pumera M: Electrochemically powered self-propelled electrophoretic nanosubmarines. Nanoscale 2010, 2:1643–1649.
6.
Wang H, Pumera M: Micro/nanomachines and living biosystems: from simple interactions to microcyborgs. Adv Funct Mater 2018, 28:1705421.
7.
Li J, Rozen I, Wang J: Rocket science at the nanoscale. ACS Nano 2016, 10:5619–5634.
8.
Xu L, Mou F, Gong H, Luo M, Guan J: Light-driven micro/nanomotors: from fundamentals to applications. Chem Soc Rev 2017, 46:6905–6926.
9.
Chen X-Z, Hoop M, Mushtaq F, Siringil E, Hu C, Nelson BJ, Pané S: Recent developments in magnetically driven microand nanorobots. Appl Mater Today 2017, 9:37–48.
10. Xu T, Xu L-P, Zhang X: Ultrasound propulsion of micro-/nanomotors. Appl Mater Today 2017, 9:493–503. 11. Wang J: Nanomachines: Fundamentals and Applications: . Weinheim, Germany: WileyVCH; 2013.
20. Gao W, Wang J: Synthetic micro/nanomotors in drug delivery. Nanoscale 2014, 6:10486–10494. 21. Peng F, Tu Y, Wilson DA: Micro/nanomotors towards in vivo application: cell, tissue and biofluid. Chem Soc Rev 2017, 46:5289–5310. 22. Li T, Chang X, Wu Z, Li J, Shao G, Deng X, Qiu J, Guo B, Zhang G, He Q, et al.: Autonomous collision-free navigation of microvehicles in complex and dynamically changing environments. ACS Nano 2017, 11:9268–9275. 23. Li J, Liu W, Li T, Rozen I, Zhao J, Bahari B, Kante B, Wang J: Swimming microrobot optical nanoscopy. Nano Lett 2016, 16:6604–6609. 24. Li J, Shklyaev OE, Li T, Liu W, Shum H, Rozen I, Balazs AC, Wang J: Self-propelled nanomotors autonomously seek and repair cracks. Nano Lett 2015, 15:7077–7085. 25. Wang H, Pumera M: Fabrication of micro/nanoscale motors. ●● Chem Rev 2015, 115:8704–8735. All fabrication methods of micromotors are included. 26. Chen C, Chang X, Angsantikul P, Li J, Esteban-Fernández de Ávila B, Karshalev E, Liu W, Mou F, He S, Castillo R, et al.: Chemotactic guidance of synthetic organic/inorganic payloads functionalized sperm micromotors. Adv Biosys 2018, 2:1700160. 27. Balasubramanian S, Kagan D, Jack Hu C-M, Campuzano S, Lobo-Castañon MJ, Lim N, Kang DY, Zimmerman M, Zhang L, Wang J: Micromachine-enabled capture and isolation of cancer cells in complex media. Angew Chem Int Ed Engl 2011, 50:4161–4164. 28. Wang H, Potroz MG, Jackman JA, Khezri B, Maric´ T, Cho N-J, Pumera M: Bioinspired spiky micromotors based on sporopollenin exine capsules. Adv Funct Mater 2017, 27:1702338. 29. Hortelão AC, Patiño T, Perez-Jiménez A, Blanco À, Sánchez S: Enzyme-powered nanobots enhance anticancer drug delivery. Adv Funct Mater 2018, 28:1705086. 30. Parmar J, Vilela D, Pellicer E, Esqué-de los Ojos D, Sort J, Sánchez S: Reusable and long-lasting active microcleaners for heterogeneous water remediation. Adv Funct Mater 2016, 26:4152–4161. 31. Li J, Singh VV, Sattayasamitsathit S, Orozco J, Kaufmann K, Dong R, Gao W, Jurado-Sanchez B, Fedorak Y, Wang J: Water-driven micromotors for rapid photocatalytic degradation of biological and chemical warfare agents. ACS Nano 2014, 8:11118–11125.
12. Gao W, Wang J: The environmental impact of micro/nanomachines: a review. ACS Nano 2014, 8:3170–3180.
32. Kim K, Guo J, Liang Z, Fan D: Artificial micro/nanomachines for bioapplications: biochemical delivery and diagnostic sensing. Adv Funct Mater 2018, 28:1705867.
13. Soler L, Sanchez S: Catalytic nanomotors for environmental monitoring and water remediation. Nanoscale 2014, 6:7175–7182.
33. Li J, de Ávila BE-F, Gao W, Zhang L, Wang J: Micro/nanorobots for biomedicine: delivery, surgery, sensing, and detoxification. Sci Robot 2017, 2:eaam6431.
14. Moo JG, Pumera M: Chemical energy powered nano/micro/macromotors and the environment. Chem Eur J 2015, 21:58–72.
34. Jurado-Sánchez B, Escarpa A: Janus micromotors for electrochemical sensing and biosensing applications: a review. Electroanalysis 2017, 29:14–23.
15. Safdar M, Simmchen J, Jänis J: Light-driven micro-and nanomotors for environmental remediation. Environ Sci: Nano 2017, 4:1602–1616.
35. Wang J: Self-propelled affinity biosensors: moving the receptor around the sample. Biosens Bioelectron 2016, 76:234–242.
16. Wang H, Khezri B, Pumera M: Catalytic DNA-functionalized self-propelled micromachines for environmental remediation. Chem 2016, 1:473–481. 17. Mou F, Pan D, Chen C, Gao Y, Xu L, Guan J: Magnetically modulated pot-like MnFe2 O4 micromotors: nanoparticle assembly fabrication and their capability for direct oil removal. Adv Funct Mater 2015, 25:6173–6181. Current Opinion in Electrochemistry 2018, 10:174–182
36. Jurado-Sánchez B, Escarpa A: Milli, micro and nanomotors: Novel analytical tools for real-world applications. TrAC Trends Anal Chem 2016, 84:48–59. 37. Campuzano S, Kagan D, Orozco J, Wang J: Motion-driven sensing and biosensing using electrochemically propelled nanomotors. Analyst 2011, 136:4621–4630.
www.sciencedirect.com
Micro- and nanorobots based sensing and biosensing Kong, Guan and Pumera
38. Duan W, Wang W, Das S, Yadav V, Mallouk TE, Sen A: Synthetic nano- and micromachines in analytical chemistry: sensing, migration, capture, delivery, and separation. Annu Rev Anal Chem 2015, 8:311–333. 39. Zha F, Wang T, Luo M, Guan J: Tubular micro/nanomotors: propulsion mechanisms, fabrication techniques and applications. Micromachines 2018, 9:78. 40. Jurado-Sánchez B, Pacheco M, Maria-Hormigos R, Escarpa A: Perspectives on janus micromotors: materials and applications. Appl Mater Today 2017, 9:407–418. 41. Kagan D, Calvo-Marzal P, Balasubramanian S, ●● Sattayasamitsathit S, Manesh KM, Flechsig G-U, Wang J: Chemical sensing based on catalytic nanomotors: motion-based detection of trace silver. J Am Chem Soc 2009, 131:12082–12083. The first demonstration of nanomotors based chemical sensing. 42. Wu J, Balasubramanian S, Kagan D, Manesh KM, Campuzano S, ● Wang J: Motion-based DNA detection using catalytic nanomotors. Nat Commun 2010, 1:36. Nucleic acid detection based on distance signals with nanomotors 43. Orozco J, García-Gradilla V, D’Agostino M, Gao W, Cortés A, Wang J: Artificial enzyme-powered microfish for water-quality testing. ACS Nano 2013, 7:818–824.
181
57. Mou F, Li Y, Chen C, Li W, Yin Y, Ma H, Guan J: Single-component TiO2 tubular microengines with motion controlled by light-induced bubbles. Small 2015, 11:2564–2570. 58. Chen C, Mou F, Xu L, Wang S, Guan J, Feng Z, Wang Q, Kong L, Li W, Wang J, et al.: Light-steered isotropic semiconductor micromotors. Adv Mater, vol 29 2017 1603374. 59. Gao W, Pei A, Dong R, Wang J: Catalytic iridium-based Janus ● micromotors powered by ultralow levels of chemical fuels. J Am Chem Soc 2014, 136:2276–2279. Catalytic micromotors can be powered by ultralow level (0.0000001%) of chemical fuels. 60. Bunea AI, Pavel IA, David S, Gaspar S: Sensing based on the motion of enzyme-modified nanorods. Biosens Bioelectron 2015, 67:42–48. 61. Schattling P, Thingholm B, Städler B: Enhanced diffusion of glucose-fueled janus particles. Chem Mater 2015, 27:7412–7418. 62. Rojas D, Jurado-Sanchez B, Escarpa A: "Shoot and Sense" janus micromotors-based strategy for the simultaneous degradation and detection of persistent organic pollutants in food and biological samples. Anal Chem 2016, 88:4153–4160.
44. Zhao G, Sanchez S, Schmidt OG, Pumera M: Poisoning of bubble propelled catalytic micromotors: the chemical environment matters. Nanoscale 2013, 5:2909–2914.
63. Moo JGS, Zhao G, Pumera M: Remote electrochemical ●● monitoring of an autonomous self-propelled capsule. J Phys Chem C 2014, 118:29896–29902. The first demonstation of motion monitor with electrochemical measurement.
45. Su Y, Ge Y, Liu L, Zhang L, Liu M, Sun Y, Zhang H, Dong B: Motion-based pH sensing based on the cartridge-case-like micromotor. ACS Appl Mater Interfaces 2016, 8:4250–4257.
64. Moo JGS, Pumera M: Self-propelled micromotors monitored by particle-electrode impact voltammetry. ACS Sensors 2016, 1:949–957.
46. Dong R, Li J, Rozen I, Ezhilan B, Xu T, Christianson C, Gao W, Saintillan D, Ren B, Wang J: Vapor-driven propulsion of catalytic micromotors. Sci Rep 2015, 5:13226.
65. Moo JGS, Mayorga-Martinez CC, Wang H, Khezri B, Teo WZ, Pumera M: Nano/microrobots meet electrochemistry. Adv Funct Mater 2017, 27:1604759.
47. Sanchez S, Soler L, Katuri J: Chemically powered micro- and nanomotors. Angew Chem Int Ed Engl 2015, 54:1414–1444.
66. Orozco J, Cheng G, Vilela D, Sattayasamitsathit S, Vazquez-Duhalt R, Valdes-Ramirez G, Pak OS, Escarpa A, Kan C, Wang J: Micromotor-based high-yielding fast oxidative detoxification of chemical threats. Angew Chem Int Ed Engl 2013, 52:13276–13279.
48. Demirok UK, Laocharoensuk R, Manesh KM, Wang J: Ultrafast catalytic alloy nanomotors. Angew Chem Int Ed Engl 2008, 47:9349–9351. 49. Van Nguyen K, Minteer SD: DNA-functionalized Pt nanoparticles as catalysts for chemically powered micromotors: toward signal-on motion-based DNA biosensor. Chem Commun 2015, 51:4782–4784. 50. Vilela D, Orozco J, Cheng G, Sattayasamitsathit S, Galarnyk M, Kan C, Wang J, Escarpa A: Multiplexed immunoassay based on micromotors and microscale tags. Lab Chip 2014, 14:3505–3509. 51. Yu X, Li Y, Wu J, Ju H: Motor-based autonomous microsensor for motion and counting immunoassay of cancer biomarker. Anal Chem 2014, 86:4501–4507. 52. Solé S, Merkoçi A, Alegret S: Determination of toxic substances based on enzyme inhibition. Part I. Electrochemical biosensors for the determination of pesticides using batch procedures. Crit Rev Anal Chem 2003, 33:89–126. 53. Besson M, Gallezot P: Deactivation of metal catalysts in liquid phase organic reactions. Catal Today 2003, 81:547–559. 54. Ma X, Wang X, Hahn K, Sanchez S: Motion control of urea-powered biocompatible hollow microcapsules. ACS Nano 2016, 10:3597–3605. 55. Moo JG, Wang H, Zhao G, Pumera M: Biomimetic artificial ● inorganic enzyme-free self-propelled microfish robot for selective detection of Pb2+ in water. Chem Eur J 2014, 20:4292–4296. Inorganic micromotors show the selective detection of heavy metal ions. 56. Guix M, Meyer AK, Koch B, Schmidt OG: Carbonate-based ● Janus micromotors moving in ultra-light acidic environment generated by HeLa cells in situ. Sci Rep 2016, 6:21701. Janus micromotors exhibit movement in extremly light acidic environment generated by HeLa cells in situ.
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67. Orozco J, Vilela D, Valdes-Ramirez G, Fedorak Y, Escarpa A, Vazquez-Duhalt R, Wang J: Efficient biocatalytic degradation of pollutants by enzyme-releasing self-propelled motors. Chem Eur J 2014, 20:2866–2871. 68. Mou F, Kong L, Chen C, Chen Z, Xu L, Guan J: Light-controlled propulsion, aggregation and separation of water-fuelled TiO2 /Pt janus submicromotors and their "on-the-fly" photocatalytic activities. Nanoscale 2016, 8:4976–4983. 69. Cinti S, Valdes-Ramirez G, Gao W, Li J, Palleschi G, Wang J: ●● Microengine-assisted electrochemical measurements at printable sensor strips. Chem Commun 2015, 51:8668–8671. Enhanced sensitivity of electrochemical detection by the motion of micromotors. 70. García-Carmona L, Moreno-Guzmán M, González MC, Escarpa A: Class enzyme-based motors for “on the fly” enantiomer analysis of amino acids. Biosens Bioelectron 2017, 96:275–280. 71. Khezri B, Sheng Moo JG, Song P, Fisher AC, Pumera M: Detecting the complex motion of self-propelled micromotors in microchannels by electrochemistry. RSC Adv 2016, 6:99977–99982. 72. Morales-Narvaez E, Guix M, Medina-Sanchez M, ● Mayorga-Martinez CC, Merkoci A: Micromotor enhanced microarray technology for protein detection. Small 2014, 10:2542–2548. Micromotors induced stirring improve the protein detection. 73. Liu M, Sun Y, Wang T, Ye Z, Zhang H, Dong B, Li CY: A biodegradable, all-polymer micromotor for gas sensing applications. J Mater Chem C 2016, 4:5945–5952.
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74. Esteban-Fernández de Ávila B, Martín A, Soto F, ●● Lopez-Ramirez MA, Campuzano S, Vásquez-Machado GM, Gao W, Zhang L, Wang J: Single cell real-time miRNAs sensing based on nanomotors. ACS Nano 2015, 9:6756–6764. Acceleration of the intracellular hybridization toward rapid miRNAs detection with nanomotors.
80. Cumming CJ, Aker C, Fisher M, Fok M, MJl Grone, Reust D, Rockley MG, Swager TM, Towers E, Williams V: Using novel fluorescent polymers as sensory materials for above-ground sensing of chemical signature compounds emanating from buried landmines. IEEE Trans Geosci Remote Sens 2001, 39:1119–1128.
75. Jurado-Sanchez B, Escarpa A, Wang J: Lighting up micromotors ● with quantum dots for smart chemical sensing. Chem Commun 2015, 51:14088–14091. Active detection of heavy metal ions with micromotors through fluorescent quenching.
81. Singh VV, Kaufmann K, Orozco J, Li J, Galarnyk M, Arya G, Wang J: Micromotor-based on-off fluorescence detection of sarin and soman simulants. Chem Commun 2015, 51:11190–11193.
76. Sentic M, Arbault S, Goudeau B, Manojlovic D, Kuhn A, Bouffier L, ● Sojic N: Electrochemiluminescent swimmers for dynamic enzymatic sensing. Chem Commun 2014, 50:10202–10205. Glucose detection with electrochemiluminescent motors. 77. Moreno-Guzman M, Jodra A, Lopez MA, Escarpa A: Self-propelled enzyme-based motors for smart mobile electrochemical and optical biosensing. Anal Chem 2015, 87:12380–12386. 78. Dale TJ, Rebek J: Fluorescent sensors for organophosphorus nerve agent mimics. J Am Chem Soc 2006, 128:4500–4501. 79. Orozco J, Cortes A, Cheng G, Sattayasamitsathit S, Gao W, Feng X, Shen Y, Wang J: Molecularly imprinted polymer-based catalytic micromotors for selective protein transport. J Am Chem Soc 2013, 135:5336–5339.
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82. Jurado-Sanchez B, Pacheco M, Rojo J, Escarpa A: Magnetocatalytic graphene quantum dots janus micromotors for bacterial endotoxin detection. Angew Chem Int Ed Engl 2017, 56:6957–6961. 83. Sentic M, Loget G, Manojlovic D, Kuhn A, Sojic N: Light-emitting electrochemical “swimmers”. Angew Chem Int Ed Engl 2012, 51:11284–11288. 84. Bouffier L, Zigah D, Adam C, Sentic M, Fattah Z, Manojlovic D, Kuhn A, Sojic N: Lighting up redox propulsion with luminol electrogenerated chemiluminescence. ChemElectroChem 2014, 1:95–98. 85. de Avila BE, Zhao M, Campuzano S, Ricci F, Pingarron JM, Mascini M, Wang J: Rapid micromotor-based naked-eye immunoassay. Talanta 2017, 167:651–657.
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Review Article Micro- and nanorobots based sensing and biosensing Lei Kong 1,3 , Jianguo Guan 3,∗ and Martin Pumera 1,2,∗ Synthetic micro- and nanorobots have attracted considerable attentions for their potential applications in environment, biomedicine and microengineering. In this review, we summarize the recent works on micro/nanorobots based sensing and biosensing according to different mechanisms: motion based sensing, electrochemical sensing with micro/nanorobots and fluorescent, electrochemiluminescent, colorimetric sensing with micro/nanorobots. Micro/nanorobots offer a convenient and active detection for nucleic acid, protein, glucose, heavy metal ions, etc. in solution and surrounding atmosphere. Furthermore, the detection sensitivity and efficiency has been significantly improved due to the stirring in solution by the motion of micro/nanorobots. Addresses 1 Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore 2 Center for the Advanced Functional Nanorobots, Department of Inorganic Chemistry, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague 6, Czech Republic 3 State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan 430070, People’s Republic of China ∗
Corresponding authors: Guan, Jianguo ([email protected]), Pumera, Martin ([email protected], [email protected])
Current Opinion in Electrochemistry 2018, 10:174–182 This review comes from a themed issue on Sensors and Biosensors
particular, due to the excellent movement, micro/nanorobots can attach to the target molecules actively and enhance the mass transfer in solution [28–32], which offers unrivaled merits in sensing and biosensing [33–40]. Herein, this article reviews the recent works on sensing and biosensing with micro/nanorobots, which can be divided into three categories according to different sensing mechanisms (Scheme 1): (1) Chemical sensing based on micro/nanorobots motion. Any changes in catalysts activity or fuels will lead to different velocities of micro/nanorobots, which can be observed for chemicals detection in solution or surrounding atmosphere; (2) Electrochemical sensing with micro/nanorobots. The chemicals in solution can be detected by electrochemical method and the detection sensitivity is enhanced due to the stirring by the motion of micro/nanorobots. Moreover, the motion of micro/nanorobots can be monitored by electrochemical changes on the electrode; (3) Fluorescent, electrochemiluminescent (ECL) and colorimetric sensing with micro/nanorobots. The motion of micro/nanorobots provides the quick detection for the change of fluorescence, electrochemiluminescence and color signals caused by the targets molecules, which is sensitive and visualized. In general, micro/nanorobots offer a convenient and active detection for nucleic acid, protein, glucose, heavy metal ions, and so on. Furthermore, the detection sensitivity and efficiency can also be improved due to the stirring and enhanced mass transfer in solution by the motion.
˘ Edited by Robert Sandulescu and Cecilia Cristea For a complete overview see the Issue and the Editorial Available online 28 June 2018 https://doi.org/10.1016/j.coelec.2018.06.004 2451-9103/© 2018 Elsevier B.V. All rights reserved.
Introduction Synthetic micro- and nanorobots can convert the energy from environment into autonomous movement, which have attracted significant attentions during last decades [1–11]. Various materials and structures were utilized to build micro/nanorobots that exhibited potential applications in environmental detection and remediation [12–18], biomedicine and microengineering [19–27]. In Current Opinion in Electrochemistry 2018, 10:174–182
Chemical sensing based on micro/nanorobots motion Catalysts and fuels are the two essential elements of catalytic micro/nanorobots [47]. Any changes in catalysts activity or fuels will lead to different velocities of micro/nanorobots, which can be observed for chemicals detection in solution. The trace silver detection with catalytic nanomotors was firstly reported by Wang and coworkers (Figure 1A) [41●● ]. According to their previous work [48], the nanowires motors will speed up by using Ag/Au alloy to replace Au segment because of the larger potential difference between Ag/Au and Pt. Thus, the Au–Pt nanomotors can speed up in H2 O2 solution with trace Ag+ present due to the deposition of silver on nanomotors. Moreover, the speed of nanomotors will decrease in solutions containing K+ , Pd2+ , Ni2+ , etc. owing to the increment of solution conductivity. Accordingly, the Au–Pt nanomotors have capacity to detect trace Ag+ in solution by observing the motion with www.sciencedirect.com
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Scheme 1
Different sensing mechanisms with micro/nanorobots.
optical microscope. Subsequently, they developed the motion-based nucleic acid detection assay, which relied on the duplex formation of nucleic acid target with thiolated Au–Pt nanomotors and silver nanoparticle tagged detector probe (Figure 1B) [42● ]. The dissolution of combined Ag nanoparticles in H2 O2 fuel will release Ag+ , which speed up the Au–Pt nanomotors. Furthermore, the velocity of Au–Pt nanomotors relates to the number of captured Ag nanoparticles, which can be adjusted by the concentration of nucleic acid targets. Finally, the resulting distance signals provided convenient measurements of nucleic acid targets at attomole level. Later, Van Nguyen and Minteer presented a new strategy for micro/nanorobots-based DNA detection [49]. The motion-based signal was produced through the attachment of DNA target modified Pt nanoparticles via specific DNA hybridization on tubular micromotors. Similarly, the micromotor-based multiplexed immunoassay for selective detection of proteins were performed by tagging the analytes with microparticles of different sizes and shapes, which helped to visualize the antibody-protein recognition [50]. At the same time, Yu et al. fabricated antibody modified micromotors for cancer biomarkers detection through selective recognition according to the decrease of velocity [51]. It is well-known that some chemicals in solution like heavy metals ions or organics may poison the catalysts [52,53], which leads to the decrease of velocity and limited lifetime of micro/nanorobots. Orozco et al. prepared catalase powered “microfish” for water testing (Figure 1C) [43]. The changes in swimming performance and lifetime of artificial microswimmers were evaluated for
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testing the toxin in water due to their inhibition to the catalase activity. Recently, Sánchez and coworkers fabricated a microcapsule motor powered by biocatalytic decomposition of urea. Ag+ or Hg2+ could be the inhibitors for affecting the enzymatic activity of urease, which enables the motors to serve as an active sensor for heavy metals [54]. Besides the enzyme-powered micromotors, Pumera and coworkers demonstrated that small molecules containing sulphur could poison Pt-catalyst micromotors because of hydroxyl radicals quenching and O2 bubbles reducing, which provides potential application of Pt-catalyst micromotors for detecting cysteine, methionine and glutathione (Figure 1D) [44]. Then, they found that Pt-based microrobots could sense the presence of Pb2+ selectively in solution [55● ]. Specifically, Pb2+ and Cd2+ can decrease the activity of Pt by attaching on the surface and covering the active sites. In addition, due to the attachment and attached area of Pb2+ is stronger and larger than that of Cd2+ , the velocity and active number of Pt-based microrobots will decrease more obviously in Pb2+ solution with low concentration. Motion-based pH sensor relies on the velocity change with variation of pH values. Guix and coworkers reported that carbonate-based Janus micromotors could move in ultra-light acidic environment (pH 6.5) generated by HeLa cells, which shows the potential ability to sense extremely light acidic environments [56● ]. Later, Su et al. developed a cartridge-case-like micromotor that consists of a gelatin shell with Pt nanoparticles decorated on inner surface. Interestingly, the wall thickness and size of opening will change with different pH values in solution, which has impact on the activity of Pt nanoparticles for decomposition of H2 O2 and bubble generation frequency from the micromotor. Finally, the velocity of micromotors will increase with increment of pH value in solution from 0 to 14 (Figure 1E), which made it possible to be a pH sensor [45]. In general, the variation of fuels will lead to the change of velocity [57,58], which can be interpreted as the output signals for fuel molecules detection. Gao et al. synthesized Ir/SiO2 Janus micromotors which could be powered at remarkably low concentration of hydrazine (0.0000001%), exhibiting the possibility to detect N2 H4 in solution by motion [59● ]. According to above study, Dong and coworkers developed the remotely triggered catalytic Ir– Au micromotors that were responsive to hydrazine vapor from the surrounding atmosphere into running solution (Figure 1F), exhibiting the capability to act as highly selective sensors for toxic gases [46]. Similarly, the enzyme substrates such as glucose, could be detected by enzymepowered mciromotors owing to the enhanced diffusivity [60,61].
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Figure 1
(A) Ag+ detection based on the motion of Au–Pt nanomotors. Reprinted with permission from ref. [41]. Copyright 2009, American Chemical Society. (B) Schematic of motion-based nucleic acid detection with Au–Pt nanomotors. Reprinted with permission from ref. [42]. Copyright 2010, Springer Nature. (C) Scheme of toxicity testing in water with catalase modified microfish. Reprinted with permission from ref. [43]. Copyright 2013, American Chemical Society. (D) Schematic demonstration of chemical sensing by poisoning Pt-catalyst microjets. Reproduced from ref. [44] with permission from the Royal Society of Chemistry. (E) pH sensing based on cartridge-case-like micromotors. Reprinted with permission from ref. [45]. Copyright 2016, American Chemical Society. (F) Gas sensing with catalytic micromotors powered by a remote fuel source [46].
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Figure 2
(A) Schematic of the Mg/Au Janus micromotors-based strategy for the simultaneous degradation/detection of DPP. Reprinted with permission from ref. [62]. Copyright 2016, American Chemical Society. (B) Scheme of electrochemical setup of the capsule track for monitoring motion. Reprinted with permission from ref. [63●● ]. Copyright 2014, American Chemical Society. (C) Schematic of a micromotor impacting a carbon microfiber electrode surface and the corresponding electrochemical signal generated. Reprinted with permission from ref. [64]. Copyright 2016, American Chemical Society.
Electrochemical sensing with micro/nanorobots Electrochemical sensing relies on the redox reaction change on the electrode or on the disturbance of the double-layer, which provides a low-cost, portable and sensitive detection method [34,65]. Meanwhile, synthetic micro/nanorobots have exhibited the ability to improve the degradation efficiency and detection sensitivity through micromixing and enhanced mass transfer by the motion [66–68]. Cinti and coworkers showed the degradation of nerve agent paraoxon with Au–Ni–Mg Janus micromotors and detection of the by-product p-nitrophenol through electrochemical detection at printable sensor strips [69●● ]. The Au–Ni–Mg Janus micromotors in 0.1 M KCl solution leads to the increment of pH, which decomposes paraoxon into p-nitrophenol. In addition, the detection sensitivity has been increased due to the stirring in solution by the motion of micromotors. Later, Escarpa and coworkers exhibited the same concept of Mg/Au Janus micromotors assisted degradation/detection of diphenyl phthalate (DPP) on disposable screen-printed electrodes (Figure 2A) [62]. More recently, they demonstrated the selective “on-the-fly” detection of D or L-amino acids with D or L-amino acid oxidase-based motors through electrochemical method [70]. The efficient movement of motors leads to the accelerated enzymatic reaction processes without the need of external stirring. Electrochemical measurement is highly sensitive that any disturbance near the electrodes can be read out as current change. Once the motor crossed the working elecwww.sciencedirect.com
trode, there was a disturbance of the electrical doublelayer and rapid increase in cathodic current (Figure 2B) [63●● ]. Therefore, the velocity of motors could be measured and the position of roadblock could be detected according to the electrochemical profiles. Later, the same group tried to monitor the motion of Janus silver micromotors and tubular Cu/Pt micromotors in the same way [64]. The catalytic micromotors passed the electrode and this will lead to the spike on chronoamperogram (Figure 2C). Additionally, the number of spikes on chronoamperogram relates to the number of active micromotors, which can be adjusted by the concentration of H2 O2 fuel. Recently, they monitored the motion of tubular micromotors over the detection electrode in the microfluidic channel [71]. The electrochemical feedback could reflect the motion of micromotors in real-time.
Fluorescent, electrochemiluminescent and colorimetric sensing with micro/nanorobots Fluorescent sensing offers high sensitivity, low-cost and operational simplicity [78]. Merkoçi and coworkers demonstrated the microarray-based immunosensing with micromotors (Figure 3A) [72● ]. The self-propelled micromotors can assist the binding between the immobilized molecular bioreceptor and target molecules in solution due to the mixing by the motion. The bound targets were revealed by the detection of antibodies labeled with fluorophore, which was measured by fluorescence intensity. Furthermore, the molecularly imprinted polymer-based catalytic micromotors for capturing and transporting proteins through selective bonding can also detect proteins Current Opinion in Electrochemistry 2018, 10:174–182
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Figure 3
(A) Microarray-based immunosensing assisted with micromotors. Reprinted with permission from ref. [72● ]. Copyright 2014, Wiley-VCH. (B) Schemes of fabrication and gas sensing of the catalase and FITC decorated PCL-SH single crystal. Reproduced with permission from ref. [73]. Copyright 2016, Royal Society of Chemistry. (C) Intracellular detection of miRNAs by US-propelled ssDNA@GO-functionalized gold nanomotors. Reprinted with permission from ref. [74●● ]. Copyright 2015, American Chemical Society. (D) Schematic of the QD-based microrockets and their ‘‘on-the-fly’’ selective detection of mercury ions based on fluorescence quenching. Reproduced with permission from ref. [75● ]. Copyright 2015, Royal Society of Chemistry. (E) Illustration of enzyme-driven ECL observed on a bipolar swimmer. Reproduced with permission from ref. [76● ]. Copyright 2014, Royal Society of Chemistry. (F) Scheme of self-propelled enzyme-based motor for hydrogen peroxide detection. Reprinted with permission from ref. [77]. Copyright 2015, American Chemical Society.
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with high efficiency in the presence of fluorescent tags [79]. Liu et al. fabricated an all-polymer micromotor that consists of biodegradation polycaprolactone single crystal and catalase, which can move in H2 O2 solution. The micromotors can detect HCl and NH3 gases after modified with fluorescein isothiocyanate (FITC) because the fluorescence intensity varies in response to different pH (Figure 3B) [73]. Fluorescence quenching methods are effective for sensitive detection based on fluorescent turn-off [80]. Wang and coworkers demonstrated the real-time intracellular biosensing of miRNA with ultrasound-propelled nanomotors (Figure 3C) [74●● ]. First, the graphene-oxide (GO) coated gold nanowires were modified with dyelabeled single-stranded DNA (ssDNA) and fluorescence signal was quenched due to the π –π interaction between GO and dye-labeled ssDNA. After the nanowires powered by ultrasound and penetrated the cancer cells, the fluorescence was recovered due to the release of dyelabeled ssDNA from the nanomotor surface through the hybridization with target miRNA. In the same way, they used the fluorophore fluoresceinamine-coated micromotors to detect nerve agents sarin and soman simulants based on fluorescent on-off [81]. The quantum dots with fluorescent property were used to detect the pollutants or toxins in solution through fluorescence quenching. Jurado-Sánchez et al. incorporated CdTe quantum dots into PEDOT/Pt tubular micromotors that exhibited “on-the-fly” Hg2+ detection (Figure 3D) [75● ]. Due to the strong affinity of Hg2+ with COOH-capped QDs and lower solubility of HgTe than CdTe, the electrons preferentially transferred from QDs to Hg2+ and alloyed Cdx Hg1-x Te was formed, which leads to the fluorescence quenching of CdTe QDs. Furthermore, the moving sensor has ability to detect Hg2+ selectively due to the slight fluorescence quenching by Cu2+ and Pb2+ ions. Very recently, they demonstrated magnetocatalytic hybrid Janus micromotors encapsulating phenylboronic acid modified graphene quantum dots for the detection of deadly bacteria endotoxins through fluorescence quenching [82]. Since Sentic and coworkers demonstrated the microswimmers propelled by bipolar electrochemistry and exhibited electrogenerated chemiluminescence (ECL) [83,84], it has attracted considerable attentions for the potential application on sensing and biosensing. Subsequently, they showed the ECL-microswimmers to monitor the glucose concentration in PBS solution (Figure 3E) [76● ]. The glucose in solution can be oxidized by glucose dehydrogenase with the conversion of NAD+ to NADH which promotes Ru(bpy)3 2+ ECL according to the classic co-reactant pathway. In addition, the ECL intensity will change with the concentration of glucose and no ECL signal appeared in the absence of glucose. www.sciencedirect.com
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Escarpa and coworkers exhibited the visual detection of H2 O2 with HRP enzyme and SDS surfactant released motor (Figure 3F) [77]. The cone shapes of the pipet tips containing SDS and HRP are propelled by the Marangoni effect. Additionally, the released HRP with H2 O2 present will oxidize TMBRED to TMBOX with blue color, which provides the method for visual detection of H2 O2 . Very recently, Wang and coworkers showed the naked-eye immunoassay of cortisol with micromotors [85]. The combination of cortisol-HRP with anti-cortisol functionalized micromotors in TMB/H2 O2 solution leads to the production of deep blue TMB that can be seen with naked eyes. In addition, the detection response and sensitivity was greatly increased by the motion of micromotors.
Conclusions and perspectives In this review, we have concluded the recent works on micro/nanorobots-based sensing and biosensing according to the mechanisms. (1) Chemical sensing based on micro/nanorobots motion. The chemicals in solution or surrounding atmosphere can be detected by the variation of micro/nanorobots velocity with microscope due to the impacts on catalysts or fuels; (2) Electrochemical sensing with micro/nanorobots. The chemicals in solution and the motion of micro/nanorobots can be detected and monitored by electrochemical changes on the electrode in real-time; (3) Fluorescent, ECL and colorimetric sensing with micro/nanorobots. The motion of micro/nanorobots offers the quick and visualized detection on the change of fluorescence, electrochemiluminescence and color signals caused by the target molecules. In general, micro/nanorobots offer an “on-the-fly” sensing and biosensing platform due to the stirring and enhanced mass transfer by the motion. Additionally, their small size and highly controlled movement make it possible to work precisely in microfluidic chips or blood vessels and in solution with microliters, which can improve the sensing and biosensing in microenvironment that the current sensing technology cannot achieve. However, there still are some issues to be solved. (1) The motion-based sensing relies on the change of velocity calculated from several motors under the observation of microscope. Accordingly, a direct method should be developed for on site interpretation. (2) Chemically powered micro/nanorobots which produce bubbles lead to the disturbance near the electrode and need additional fuels, which may bring interferences to the assay. Thus, fuel-free micro/nanorobotsbased sensing should be more appropriate. (3) The fabrication of micro/nanorobots should be uniform, which makes the motion more stable and the detection results more standard and repeatable. (4) In order to compare against other biosensing strategies, the detection sensitivity and accuracy should be further improved for the commercialization in the future. Currently, micro/nanorobots have advantages in microenvironmental sensing. Current Opinion in Electrochemistry 2018, 10:174–182
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Conflict of interest The authors declare no competing financial interest.
18. Parmar J, Villa K, Vilela D, Sánchez S: Platinum-free cobalt ferrite based micromotors for antibiotic removal. Appl Mater Today 2017, 9:605–611.
Acknowledgments
19. Wang J, Gao W: Nano/microscale motors: biomedical opportunities and challenges. ACS Nano 2012, 6:5745–5751.
Authors acknowledge A∗ Star grant SERC A1783c0005 (Singapore) and the National Natural Science Foundation of China (21474078 and 51521001). L. K. acknowledges the Scholarship Fund from China Scholarship Council (CSC No. 201606950043). This work was supported by the project Advanced Functional Nanorobots (reg. No. CZ.02.1.01/0.0/0.0/15_003/0000444 financed by the EFRR) by Czech Republic.
References and recommended reading Papers of particular interest, published within the period of review, have been highlighted as: •
Paper of special interest. Paper of outstanding interest.
••
1.
Paxton WF, Sundararajan S, Mallouk TE, Sen A: Chemical locomotion. Angew Chem Int Ed Engl 2006, 45:5420–5429.
2.
Sengupta S, Ibele ME, Sen A: Fantastic voyage: designing self-powered nanorobots. Angew Chem Int Ed Engl 2012, 51:8434–8445.
3. Guix M, Mayorga-Martinez CC, Merkoci A: Nano/micromotors in ●● (bio)chemical science applications. Chem Rev 2014, 114:6285–6322. All motion mechanisms of nano/micromotors are discussed. 4.
Dey KK, Sen A: Chemically propelled molecules and machines. J Am Chem Soc 2017, 139:7666–7676.
5.
Pumera M: Electrochemically powered self-propelled electrophoretic nanosubmarines. Nanoscale 2010, 2:1643–1649.
6.
Wang H, Pumera M: Micro/nanomachines and living biosystems: from simple interactions to microcyborgs. Adv Funct Mater 2018, 28:1705421.
7.
Li J, Rozen I, Wang J: Rocket science at the nanoscale. ACS Nano 2016, 10:5619–5634.
8.
Xu L, Mou F, Gong H, Luo M, Guan J: Light-driven micro/nanomotors: from fundamentals to applications. Chem Soc Rev 2017, 46:6905–6926.
9.
Chen X-Z, Hoop M, Mushtaq F, Siringil E, Hu C, Nelson BJ, Pané S: Recent developments in magnetically driven microand nanorobots. Appl Mater Today 2017, 9:37–48.
10. Xu T, Xu L-P, Zhang X: Ultrasound propulsion of micro-/nanomotors. Appl Mater Today 2017, 9:493–503. 11. Wang J: Nanomachines: Fundamentals and Applications: . Weinheim, Germany: WileyVCH; 2013.
20. Gao W, Wang J: Synthetic micro/nanomotors in drug delivery. Nanoscale 2014, 6:10486–10494. 21. Peng F, Tu Y, Wilson DA: Micro/nanomotors towards in vivo application: cell, tissue and biofluid. Chem Soc Rev 2017, 46:5289–5310. 22. Li T, Chang X, Wu Z, Li J, Shao G, Deng X, Qiu J, Guo B, Zhang G, He Q, et al.: Autonomous collision-free navigation of microvehicles in complex and dynamically changing environments. ACS Nano 2017, 11:9268–9275. 23. Li J, Liu W, Li T, Rozen I, Zhao J, Bahari B, Kante B, Wang J: Swimming microrobot optical nanoscopy. Nano Lett 2016, 16:6604–6609. 24. Li J, Shklyaev OE, Li T, Liu W, Shum H, Rozen I, Balazs AC, Wang J: Self-propelled nanomotors autonomously seek and repair cracks. Nano Lett 2015, 15:7077–7085. 25. Wang H, Pumera M: Fabrication of micro/nanoscale motors. ●● Chem Rev 2015, 115:8704–8735. All fabrication methods of micromotors are included. 26. Chen C, Chang X, Angsantikul P, Li J, Esteban-Fernández de Ávila B, Karshalev E, Liu W, Mou F, He S, Castillo R, et al.: Chemotactic guidance of synthetic organic/inorganic payloads functionalized sperm micromotors. Adv Biosys 2018, 2:1700160. 27. Balasubramanian S, Kagan D, Jack Hu C-M, Campuzano S, Lobo-Castañon MJ, Lim N, Kang DY, Zimmerman M, Zhang L, Wang J: Micromachine-enabled capture and isolation of cancer cells in complex media. Angew Chem Int Ed Engl 2011, 50:4161–4164. 28. Wang H, Potroz MG, Jackman JA, Khezri B, Maric´ T, Cho N-J, Pumera M: Bioinspired spiky micromotors based on sporopollenin exine capsules. Adv Funct Mater 2017, 27:1702338. 29. Hortelão AC, Patiño T, Perez-Jiménez A, Blanco À, Sánchez S: Enzyme-powered nanobots enhance anticancer drug delivery. Adv Funct Mater 2018, 28:1705086. 30. Parmar J, Vilela D, Pellicer E, Esqué-de los Ojos D, Sort J, Sánchez S: Reusable and long-lasting active microcleaners for heterogeneous water remediation. Adv Funct Mater 2016, 26:4152–4161. 31. Li J, Singh VV, Sattayasamitsathit S, Orozco J, Kaufmann K, Dong R, Gao W, Jurado-Sanchez B, Fedorak Y, Wang J: Water-driven micromotors for rapid photocatalytic degradation of biological and chemical warfare agents. ACS Nano 2014, 8:11118–11125.
12. Gao W, Wang J: The environmental impact of micro/nanomachines: a review. ACS Nano 2014, 8:3170–3180.
32. Kim K, Guo J, Liang Z, Fan D: Artificial micro/nanomachines for bioapplications: biochemical delivery and diagnostic sensing. Adv Funct Mater 2018, 28:1705867.
13. Soler L, Sanchez S: Catalytic nanomotors for environmental monitoring and water remediation. Nanoscale 2014, 6:7175–7182.
33. Li J, de Ávila BE-F, Gao W, Zhang L, Wang J: Micro/nanorobots for biomedicine: delivery, surgery, sensing, and detoxification. Sci Robot 2017, 2:eaam6431.
14. Moo JG, Pumera M: Chemical energy powered nano/micro/macromotors and the environment. Chem Eur J 2015, 21:58–72.
34. Jurado-Sánchez B, Escarpa A: Janus micromotors for electrochemical sensing and biosensing applications: a review. Electroanalysis 2017, 29:14–23.
15. Safdar M, Simmchen J, Jänis J: Light-driven micro-and nanomotors for environmental remediation. Environ Sci: Nano 2017, 4:1602–1616.
35. Wang J: Self-propelled affinity biosensors: moving the receptor around the sample. Biosens Bioelectron 2016, 76:234–242.
16. Wang H, Khezri B, Pumera M: Catalytic DNA-functionalized self-propelled micromachines for environmental remediation. Chem 2016, 1:473–481. 17. Mou F, Pan D, Chen C, Gao Y, Xu L, Guan J: Magnetically modulated pot-like MnFe2 O4 micromotors: nanoparticle assembly fabrication and their capability for direct oil removal. Adv Funct Mater 2015, 25:6173–6181. Current Opinion in Electrochemistry 2018, 10:174–182
36. Jurado-Sánchez B, Escarpa A: Milli, micro and nanomotors: Novel analytical tools for real-world applications. TrAC Trends Anal Chem 2016, 84:48–59. 37. Campuzano S, Kagan D, Orozco J, Wang J: Motion-driven sensing and biosensing using electrochemically propelled nanomotors. Analyst 2011, 136:4621–4630.
www.sciencedirect.com
Micro- and nanorobots based sensing and biosensing Kong, Guan and Pumera
38. Duan W, Wang W, Das S, Yadav V, Mallouk TE, Sen A: Synthetic nano- and micromachines in analytical chemistry: sensing, migration, capture, delivery, and separation. Annu Rev Anal Chem 2015, 8:311–333. 39. Zha F, Wang T, Luo M, Guan J: Tubular micro/nanomotors: propulsion mechanisms, fabrication techniques and applications. Micromachines 2018, 9:78. 40. Jurado-Sánchez B, Pacheco M, Maria-Hormigos R, Escarpa A: Perspectives on janus micromotors: materials and applications. Appl Mater Today 2017, 9:407–418. 41. Kagan D, Calvo-Marzal P, Balasubramanian S, ●● Sattayasamitsathit S, Manesh KM, Flechsig G-U, Wang J: Chemical sensing based on catalytic nanomotors: motion-based detection of trace silver. J Am Chem Soc 2009, 131:12082–12083. The first demonstration of nanomotors based chemical sensing. 42. Wu J, Balasubramanian S, Kagan D, Manesh KM, Campuzano S, ● Wang J: Motion-based DNA detection using catalytic nanomotors. Nat Commun 2010, 1:36. Nucleic acid detection based on distance signals with nanomotors 43. Orozco J, García-Gradilla V, D’Agostino M, Gao W, Cortés A, Wang J: Artificial enzyme-powered microfish for water-quality testing. ACS Nano 2013, 7:818–824.
181
57. Mou F, Li Y, Chen C, Li W, Yin Y, Ma H, Guan J: Single-component TiO2 tubular microengines with motion controlled by light-induced bubbles. Small 2015, 11:2564–2570. 58. Chen C, Mou F, Xu L, Wang S, Guan J, Feng Z, Wang Q, Kong L, Li W, Wang J, et al.: Light-steered isotropic semiconductor micromotors. Adv Mater, vol 29 2017 1603374. 59. Gao W, Pei A, Dong R, Wang J: Catalytic iridium-based Janus ● micromotors powered by ultralow levels of chemical fuels. J Am Chem Soc 2014, 136:2276–2279. Catalytic micromotors can be powered by ultralow level (0.0000001%) of chemical fuels. 60. Bunea AI, Pavel IA, David S, Gaspar S: Sensing based on the motion of enzyme-modified nanorods. Biosens Bioelectron 2015, 67:42–48. 61. Schattling P, Thingholm B, Städler B: Enhanced diffusion of glucose-fueled janus particles. Chem Mater 2015, 27:7412–7418. 62. Rojas D, Jurado-Sanchez B, Escarpa A: "Shoot and Sense" janus micromotors-based strategy for the simultaneous degradation and detection of persistent organic pollutants in food and biological samples. Anal Chem 2016, 88:4153–4160.
44. Zhao G, Sanchez S, Schmidt OG, Pumera M: Poisoning of bubble propelled catalytic micromotors: the chemical environment matters. Nanoscale 2013, 5:2909–2914.
63. Moo JGS, Zhao G, Pumera M: Remote electrochemical ●● monitoring of an autonomous self-propelled capsule. J Phys Chem C 2014, 118:29896–29902. The first demonstation of motion monitor with electrochemical measurement.
45. Su Y, Ge Y, Liu L, Zhang L, Liu M, Sun Y, Zhang H, Dong B: Motion-based pH sensing based on the cartridge-case-like micromotor. ACS Appl Mater Interfaces 2016, 8:4250–4257.
64. Moo JGS, Pumera M: Self-propelled micromotors monitored by particle-electrode impact voltammetry. ACS Sensors 2016, 1:949–957.
46. Dong R, Li J, Rozen I, Ezhilan B, Xu T, Christianson C, Gao W, Saintillan D, Ren B, Wang J: Vapor-driven propulsion of catalytic micromotors. Sci Rep 2015, 5:13226.
65. Moo JGS, Mayorga-Martinez CC, Wang H, Khezri B, Teo WZ, Pumera M: Nano/microrobots meet electrochemistry. Adv Funct Mater 2017, 27:1604759.
47. Sanchez S, Soler L, Katuri J: Chemically powered micro- and nanomotors. Angew Chem Int Ed Engl 2015, 54:1414–1444.
66. Orozco J, Cheng G, Vilela D, Sattayasamitsathit S, Vazquez-Duhalt R, Valdes-Ramirez G, Pak OS, Escarpa A, Kan C, Wang J: Micromotor-based high-yielding fast oxidative detoxification of chemical threats. Angew Chem Int Ed Engl 2013, 52:13276–13279.
48. Demirok UK, Laocharoensuk R, Manesh KM, Wang J: Ultrafast catalytic alloy nanomotors. Angew Chem Int Ed Engl 2008, 47:9349–9351. 49. Van Nguyen K, Minteer SD: DNA-functionalized Pt nanoparticles as catalysts for chemically powered micromotors: toward signal-on motion-based DNA biosensor. Chem Commun 2015, 51:4782–4784. 50. Vilela D, Orozco J, Cheng G, Sattayasamitsathit S, Galarnyk M, Kan C, Wang J, Escarpa A: Multiplexed immunoassay based on micromotors and microscale tags. Lab Chip 2014, 14:3505–3509. 51. Yu X, Li Y, Wu J, Ju H: Motor-based autonomous microsensor for motion and counting immunoassay of cancer biomarker. Anal Chem 2014, 86:4501–4507. 52. Solé S, Merkoçi A, Alegret S: Determination of toxic substances based on enzyme inhibition. Part I. Electrochemical biosensors for the determination of pesticides using batch procedures. Crit Rev Anal Chem 2003, 33:89–126. 53. Besson M, Gallezot P: Deactivation of metal catalysts in liquid phase organic reactions. Catal Today 2003, 81:547–559. 54. Ma X, Wang X, Hahn K, Sanchez S: Motion control of urea-powered biocompatible hollow microcapsules. ACS Nano 2016, 10:3597–3605. 55. Moo JG, Wang H, Zhao G, Pumera M: Biomimetic artificial ● inorganic enzyme-free self-propelled microfish robot for selective detection of Pb2+ in water. Chem Eur J 2014, 20:4292–4296. Inorganic micromotors show the selective detection of heavy metal ions. 56. Guix M, Meyer AK, Koch B, Schmidt OG: Carbonate-based ● Janus micromotors moving in ultra-light acidic environment generated by HeLa cells in situ. Sci Rep 2016, 6:21701. Janus micromotors exhibit movement in extremly light acidic environment generated by HeLa cells in situ.
www.sciencedirect.com
67. Orozco J, Vilela D, Valdes-Ramirez G, Fedorak Y, Escarpa A, Vazquez-Duhalt R, Wang J: Efficient biocatalytic degradation of pollutants by enzyme-releasing self-propelled motors. Chem Eur J 2014, 20:2866–2871. 68. Mou F, Kong L, Chen C, Chen Z, Xu L, Guan J: Light-controlled propulsion, aggregation and separation of water-fuelled TiO2 /Pt janus submicromotors and their "on-the-fly" photocatalytic activities. Nanoscale 2016, 8:4976–4983. 69. Cinti S, Valdes-Ramirez G, Gao W, Li J, Palleschi G, Wang J: ●● Microengine-assisted electrochemical measurements at printable sensor strips. Chem Commun 2015, 51:8668–8671. Enhanced sensitivity of electrochemical detection by the motion of micromotors. 70. García-Carmona L, Moreno-Guzmán M, González MC, Escarpa A: Class enzyme-based motors for “on the fly” enantiomer analysis of amino acids. Biosens Bioelectron 2017, 96:275–280. 71. Khezri B, Sheng Moo JG, Song P, Fisher AC, Pumera M: Detecting the complex motion of self-propelled micromotors in microchannels by electrochemistry. RSC Adv 2016, 6:99977–99982. 72. Morales-Narvaez E, Guix M, Medina-Sanchez M, ● Mayorga-Martinez CC, Merkoci A: Micromotor enhanced microarray technology for protein detection. Small 2014, 10:2542–2548. Micromotors induced stirring improve the protein detection. 73. Liu M, Sun Y, Wang T, Ye Z, Zhang H, Dong B, Li CY: A biodegradable, all-polymer micromotor for gas sensing applications. J Mater Chem C 2016, 4:5945–5952.
Current Opinion in Electrochemistry 2018, 10:174–182
182
Sensors and Biosensors
74. Esteban-Fernández de Ávila B, Martín A, Soto F, ●● Lopez-Ramirez MA, Campuzano S, Vásquez-Machado GM, Gao W, Zhang L, Wang J: Single cell real-time miRNAs sensing based on nanomotors. ACS Nano 2015, 9:6756–6764. Acceleration of the intracellular hybridization toward rapid miRNAs detection with nanomotors.
80. Cumming CJ, Aker C, Fisher M, Fok M, MJl Grone, Reust D, Rockley MG, Swager TM, Towers E, Williams V: Using novel fluorescent polymers as sensory materials for above-ground sensing of chemical signature compounds emanating from buried landmines. IEEE Trans Geosci Remote Sens 2001, 39:1119–1128.
75. Jurado-Sanchez B, Escarpa A, Wang J: Lighting up micromotors ● with quantum dots for smart chemical sensing. Chem Commun 2015, 51:14088–14091. Active detection of heavy metal ions with micromotors through fluorescent quenching.
81. Singh VV, Kaufmann K, Orozco J, Li J, Galarnyk M, Arya G, Wang J: Micromotor-based on-off fluorescence detection of sarin and soman simulants. Chem Commun 2015, 51:11190–11193.
76. Sentic M, Arbault S, Goudeau B, Manojlovic D, Kuhn A, Bouffier L, ● Sojic N: Electrochemiluminescent swimmers for dynamic enzymatic sensing. Chem Commun 2014, 50:10202–10205. Glucose detection with electrochemiluminescent motors. 77. Moreno-Guzman M, Jodra A, Lopez MA, Escarpa A: Self-propelled enzyme-based motors for smart mobile electrochemical and optical biosensing. Anal Chem 2015, 87:12380–12386. 78. Dale TJ, Rebek J: Fluorescent sensors for organophosphorus nerve agent mimics. J Am Chem Soc 2006, 128:4500–4501. 79. Orozco J, Cortes A, Cheng G, Sattayasamitsathit S, Gao W, Feng X, Shen Y, Wang J: Molecularly imprinted polymer-based catalytic micromotors for selective protein transport. J Am Chem Soc 2013, 135:5336–5339.
Current Opinion in Electrochemistry 2018, 10:174–182
82. Jurado-Sanchez B, Pacheco M, Rojo J, Escarpa A: Magnetocatalytic graphene quantum dots janus micromotors for bacterial endotoxin detection. Angew Chem Int Ed Engl 2017, 56:6957–6961. 83. Sentic M, Loget G, Manojlovic D, Kuhn A, Sojic N: Light-emitting electrochemical “swimmers”. Angew Chem Int Ed Engl 2012, 51:11284–11288. 84. Bouffier L, Zigah D, Adam C, Sentic M, Fattah Z, Manojlovic D, Kuhn A, Sojic N: Lighting up redox propulsion with luminol electrogenerated chemiluminescence. ChemElectroChem 2014, 1:95–98. 85. de Avila BE, Zhao M, Campuzano S, Ricci F, Pingarron JM, Mascini M, Wang J: Rapid micromotor-based naked-eye immunoassay. Talanta 2017, 167:651–657.
www.sciencedirect.com