Molecular Memory Micromotors for Fast Snake Venom Toxin Dynamic Detection.

The analysis and detection of snake venom toxins are a matter of great importance in clinical diagnosis for fast treatment and the discovery of new pharmaceutical products. Current detection methods have high associated costs and require the use of sophisticated bioreceptors, which in some cases are difficult to obtain. Herein, we report the synthesis of template-based molecularly imprinted micromotors for dynamic detection of α-bungarotoxin as a model toxin present in the venom of many-banded krait (Bungarus multicinctus). The specific recognition sites are built-in in the micromotors by incubation of the membrane template with the target toxin, followed by a controlled electrodeposition of a poly(3,4-ethylenedioxythiophene)/poly(sodium 4-styrenesulfonate) polymeric layer, a magnetic Ni layer to promote magnetic guidance and facilitate washing steps, and a Pt layer for autonomous propulsion in the presence of hydrogen peroxide. The enhanced fluid mixing and autonomous propulsion increase the likelihood of interactions with the target analyte as compared with static counterparts, retaining the tetramethylrhodamine-labeled α-bungarotoxin on the micromotor surface with extremely fast dynamic sensor response (after just 20 s navigation) in only 3 µL of water, urine, or serum samples. The sensitivity achieved meets the clinically relevant concentration postsnakebite (from 0.1 to 100 µg/mL), illustrating the feasibility of the approach for practical applications. The selectivity of the protocol is very high, as illustrated by the absence of fluorescence in the micromotor surface in the presence of α-cobratoxin as a representative toxin with a size and structure similar to those of α-bungarotoxin. Recoveries higher than 95% are obtained in the analysis of urine- and serum-fortified samples. The new strategy holds considerable promise for fast, inexpensive, and even onsite detection of several toxins using multiple molecularly imprinted micromotors with tailored recognition abilities.

Prussian Blue/Chitosan Micromotors with Intrinsic Enzyme-like Activity for (bio)-Sensing Assays.

Prussian Blue (PB)/chitosan enzyme mimetic tubular micromotors are used here for on-the-fly (bio)-sensing assays. The micromotors are easily prepared by direct deposition of chitosan into the pores of a membrane template and in situ PB synthesis during hydrogel deposition. Under judicious pH control, PB micromotors display enzyme mimetic capabilities with three key functions on board: the autonomous oxygen bubble propulsion (with PB acting as a catalase mimic for hydrogen peroxide decomposition), 3,3',5,5'-tetramethylbenzidine (TMB) oxidation (with PB acting as a peroxidase mimic for analyte detection), and as a magnetic material (to simplify the (bio)-sensing steps). In connection with chitosan capabilities, these unique enzyme mimetic micromotors are further functionalized with acetylthiocholinesterase enzyme (ATChE) to be explored in fast inhibition assays (20 min) for the colorimetric determination of the nerve agent neostigmine, with excellent analytical performance in terms of quantification limit (0.30 µM) and concentration linear range (up to 500 µM), without compromising efficient micromotor propulsion. The new concept illustrated holds considerable potential for a myriad of (bio)-sensing applications, including forensics, where this conceptual approach remains to be explored. Micromotor-based tests to be used in crime scenes are also envisioned due to the reliable neostigmine determination in unpretreated samples.

MoSBOTs: Magnetically Driven Biotemplated MoS2 -Based Microrobots for Biomedical Applications.

2D layered molybdenum disulfide (MoS2 ) nanomaterials are a promising platform for biomedical applications, particularly due to its high biocompatibility characteristics, mechanical and electrical properties, and flexible functionalization. Additionally, the bandgap of MoS2 can be engineered to absorb light over a wide range of wavelengths, which can then be transformed into local heat for applications in photothermal tissue ablation and regeneration. However, limitations such as poor stability of aqueous dispersions and low accumulation in affected tissues impair the full realization of MoS2 for biomedical applications. To overcome such challenges, herein, multifunctional MoS2 -based magnetic helical microrobots (MoSBOTs) using cyanobacterium Spirulina platensis are proposed as biotemplate for therapeutic and biorecognition applications. The cytocompatible microrobots combine remote magnetic navigation with MoS2 photothermal activity under near-infrared irradiation. The resulting photoabsorbent features of the MoSBOTs are exploited for targeted photothermal ablation of cancer cells and on-the-fly biorecognition in minimally invasive oncotherapy applications. The proposed multi-therapeutic MoSBOTs hold considerable potential for a myriad of cancer treatment and diagnostic-related applications, circumventing current challenges of ablative procedures.

Biocompatible micromotors for biosensing.

Micro/nanomotors are nanoscale devices that have been explored in various fields, such as drug delivery, environmental remediation, or biosensing and diagnosis. The use of micro/nanomotors has grown considerably over the past few years, partially because of the advantages that they offer in the development of new conceptual avenues in biosensing. This is due to their propulsion and intermixing in solution compared with their respective static forms, which enables motion-based detection methods and/or decreases bioassay time. This review focuses on the impacts of micro/nanomotors on biosensing research in the last 2 years. An overview of designs for bioreceptor attachment to micro/nanomotors is given. Recent developments have focused on chemically propelled micromotors using external fuels, commonly hydrogen peroxide. However, the associated fuel toxicity and inconvenience of use in relevant biological samples such as blood have prompted researchers to explore new micro/nanomotor biosensing approaches based on biocompatible propulsion sources such as magnetic or ultrasound fields. The main advances in biocompatible propulsion sources for micro/nanomotors as novel biosensing platforms are discussed and grouped by their propulsion-driven forces. The relevant analytical applications are discussed and representatively illustrated. Moreover, envisioning future biosensing applications, the principal advantages of micro/nanomotor synthesis using biocompatible and biodegradable materials are given. The review concludes with a realistic drawing on the present and future perspectives.

Nanomaterials meet surface-enhanced Raman scattering towards enhanced clinical diagnosis: a review.

Surface-enhanced Raman scattering (SERS) is a very promising tool for the direct detection of biomarkers for the diagnosis of i.e., cancer and pathogens. Yet, current SERS strategies are hampered by non-specific interactions with co-existing substances in the biological matrices and the difficulties of obtaining molecular fingerprint information from the complex vibrational spectrum. Raman signal enhancement is necessary, along with convenient surface modification and machine-based learning to address the former issues. This review aims to describe recent advances and prospects in SERS-based approaches for cancer and pathogens diagnosis. First, direct SERS strategies for key biomarker sensing, including the use of substrates such as plasmonic, semiconductor structures, and 3D order nanostructures for signal enhancement will be discussed. Secondly, we will illustrate recent advances for indirect diagnosis using active nanomaterials, Raman reporters, and specific capture elements as SERS tags. Thirdly, critical challenges for translating the potential of the SERS sensing techniques into clinical applications via machine learning and portable instrumentation will be described. The unique nature and integrated sensing capabilities of SERS provide great promise for early cancer diagnosis or fast pathogens detection, reducing sanitary costs but most importantly allowing disease prevention and decreasing mortality rates.

Transition metal dichalcogenide-based Janus micromotors for on-the-fly Salmonella detection.

Janus micromotors encapsulating transition metal dichalcogenides (TMDs) and modified with a rhodamine (RhO)-labeled affinity peptide (RhO-NFMESLPRLGMH) are used here for Salmonella enterica endotoxin detection. The OFF-ON strategy relies on the specific binding of the peptide with the TMDs to induce fluorescence quenching (OFF state); which is next recovered due to selectively binding to the endotoxin (ON state). The increase in the fluorescence of the micromotors can be quantified as a function of the concentration of endotoxin in the sample. The developed strategy was applied to the determination of Salmonella enterica serovar Typhimurium endotoxin with high sensitivity (limits of detection (LODs) of 2.0 µg/mL using MoS2, and 1.2 µg/mL using WS2), with quantitative recoveries (ranging from 93.7 ± 4.6 % to 94.3 ± 6.6%) in bacteria cultures in just 5 min. No fluorescence recovery is observed in the presence of endotoxins with a similar structure, illustrating the high selectivity of the protocol, even against endotoxins of Salmonella enterica serovar Enteritidis with great similarity in its structure, demonstrating the high bacterial specificity of the developed method. These results revealed the analytical potential of the reported strategy in multiplexed assays using different receptors or in the design of portable detection devices.

Remote Teaching of Chemistry Laboratory Courses during COVID-19.

This paper describes the transfer from face-to-face education to emergency remote teaching of chemistry laboratory courses in a bachelor's degree in Pharmacy during the COVID-19 pandemic. The virtualization was carried out using videos of each experimental practice and questionnaires containing the experimental data needed. The contents were integrated into the virtual platform Blackboard Collaborate, where tutorials and remote support from the teachers were provided to solve the issues raised. The didactic strategy was very positive: it turned the students into active learners, fostering knowledge sharing and promoting the self-management of their learning process. The teachers acted as guides, raising questions, and provided continuous feedback to the students that contributed to knowledge assimilation and competence acquisition. The teaching-learning process was evaluated through a rubric that graded the reports delivered by the students and a final online test. The impact of this teaching methodology was assessed by comparing the students' marks with those obtained in the conventional on-site education before the pandemic and feedback from the students via surveys. This study provides a unique experience on how a traditional instruction can be adapted to remote teaching in analytical chemistry laboratories, providing new tools that can be used in future pandemics or in other settings.

Smartphone-Based Janus Micromotors Strategy for Motion-Based Detection of Glutathione.

Herein, we describe a Janus micromotor smartphone platform for the motion-based detection of glutathione. The system compromises a universal three-dimensional (3D)-printed platform to hold a commercial smartphone, which is equipped with an external magnification optical lens (20-400×) directly attached to the camera, an adjustable sample holder to accommodate a glass slide, and a light-emitting diode (LED) source. The presence of glutathione in peroxide-rich sample media results in the decrease in the speed of 20 µm graphene-wrapped/PtNPs Janus micromotors due to poisoning of the catalytic layer by a thiol bond formation. The speed can be correlated with the concentration of glutathione, achieving a limit of detection of 0.90 µM, with percent recoveries and excellent selectivity under the presence of interfering amino acids and proteins. Naked-eye visualization of the speed decrease allows for the design of a test strip for fast glutathione detection (30 s), avoiding previous amplification strategies or sample preparation steps. The concept can be extended to other micromotor approaches relying on fluorescence or colorimetric detection for future multiplexed schemes.

Janus particles and motors: unrivaled devices for mastering (bio)sensing.

Janus particles are a unique type of materials combining two different functionalities in a single unit. This allows the combination of different analytical properties leading to new analytical capabilities, i.e., enhanced fluid mixing to increase sensitivity with targeting capturing abilities and unique advantages in terms of multi-functionality and versatility of modification, use, and operation both in static and dynamic modes. The aim of this conceptual review is to cover recent (over the last 5 years) advances in the use of Janus microparticles and micromotors in (bio)-sensing. First, the role of different materials and synthetic routes in the performance of Janus particles are described. In a second main section, electrochemical and optical biosensing based on Janus particles and motors are covered, including in vivo and in vitro methodologies as the next biosensing generation. Current challenges and future perspectives are provided in the conclusions section.

Dual-Propelled Lanbiotic Based Janus Micromotors for Selective Inactivation of Bacterial Biofilms.

Graphene oxide/PtNPs/Fe2 O3 "dual-propelled" catalytic and fuel-free rotary actuated magnetic Janus micromotors modified with the lanbiotic Nisin are used for highly selective capture/inactivation of gram-positive bacteria units and biofilms. Specific interaction of Nisin with the Lipid II unit of Staphylococcus Aureus bacteria in connection with the enhanced micromotor movement and generated fluid flow result in a 2-fold increase of the capture/killing ability (both in bubble and magnetic propulsion modes) as compared with free peptide and static counterparts. The high stability of Nisin along with the high towing force of the micromotors allow for efficient operation in untreated raw media (tap water, juice and serum) and even in blood and in flowing blood in magnetic mode. The high selectivity of the approach is illustrated by the dramatically lower interaction with gram-negative bacteria (Escherichia Coli). The double-propulsion (catalytic or fuel-free magnetic) mode of the micromotors and the high biocompatibility holds considerable promise to design micromotors with tailored lanbiotics that can response to the changes that make the bacteria resistant in a myriad of clinical, environmental remediation or food safety applications.

Chalcogenides-based Tubular Micromotors in Fluorescent Assays.

WS2/Pt and MoS2/Pt bubble propelled micromotors are used as "on-the-fly" sensing platforms in bioassays, using a highly selective affinity peptide probe for "OFF-ON" detection of Escherichia coli as a model endotoxin. The different outer micromotor surface characteristics play an important role in the sensing performance. The relatively high outer surface of WS2/Pt micromotors results in a 3.5-fold increase in sensitivity compared to MoS2/Pt micromotors due to enhanced peptide probe loading and release. The peptide-modified WS2 micromotors are used as a low-cost and high-throughput approach for the determination of E. coli endotoxin after only 60 s, with a limit of detection of 1.9 ng mL-1 and high selectivity. The method has been validated using spiked samples (tap water, blood serum, and saliva) and bacteria media (blank broth, Staphylococcus aureus, and E. coli). The concept can be extended to the analysis of other (bio)-analytes and easily incorporated into portable instrumentation, holding great promise in a myriad of clinical, environmental, or food-safety applications.

Nano/Micromotors for Diagnosis and Therapy of Cancer and Infectious Diseases.

Micromotors are man-made nano/microscale devices capable of transforming energy into mechanical motion. The accessibility and force offered by micromotors hold great promise to solve complex biomedical challenges. This Review highlights current progress and prospects in the use of nano and micromotors for diagnosis and treatment of infectious diseases and cancer. Motion-based sensing and fluorescence switching detection strategies along with therapeutic approaches based on direct cell capture; killing by direct contact or specific drug delivery to the affected site, will be comprehensively covered. Future challenges to translate the potential of nano/micromotors into practical applications will be described in the conclusions.

Graphdiyne Micromotors in Living Biomedia.

Graphdiyne (GDY), a new kind of two-dimensional (2D) material, was combined with micromotor technology for "on-the-fly" operations in complex biomedia. Microtubular structures were prepared by template deposition on membrane templates, resulting in functional structures rich in sp and sp2 carbons with highly conjugated π networks. This resulted in a highly increased surface area for a higher loading of anticancer drugs or enhanced quenching ability over other 2D based micromotors, such as graphene oxide (GO) or smooth tubular micromotors. High biocompatibility with almost 100 % cell viability was observed in cytotoxicity assays with moving micromotors in the presence of HeLa cells. On a first example, GDY micromotors loaded with doxorubicin (DOX) were used for pH responsive release and HeLa cancer cells killing. The use of affinity peptide engineered GDY micromotors was also illustrated for highly sensitive and selective fluorescent OFF-ON detection of cholera toxin B through specific recognition of the subunit B region of the target toxin. The new developments illustrated here offer considerable promise for the use of GDY as part of micromotors in living biosystems.

Light-driven nanomotors and micromotors: envisioning new analytical possibilities for bio-sensing.

The aim of this conceptual review is to cover recent developments of light-propelled micromotors for analytical (bio)-sensing. Challenges of self-propelled light-driven micromotors in complex (biological) media and potential solutions from material aspects and propulsion mechanism to achieve final analytical detection for in vivo and in vitro applications will be comprehensively covered. Graphical abstract.

Magnetic Fields Enhanced the Performance of Tubular Dichalcogenide Micromotors at Low Hydrogen Peroxide Levels.

Propulsion at the microscale has attracted significant research interest. In this work, a numerical simulation to explain the speed boost of up to 34 % experienced by transition metal dichalcogenides (TMD) based micromotors under the effect of applied magnetic fields is described. The simulations show that, when an external magnetic field is applied, the flow regime changes from turbulent to laminar. This causes an increase in the residence time of the fuel over the catalyst surface, which enhances the oxygen production. The more efficient generation and growth of the bubbles lead to an increase of the capillary force exerted by them. Interestingly, the effect is more pronounced as the level of fuel decrease. The validity of the model is also proven by comparing both theoretical and experimental results. Interestingly, the speed enhancement in magnetic mode depends on geometrical factors only, as a similar phenomenon was observed in a variety of microjets with a variable surface roughness. The understanding of such phenomena will open new avenues for understanding and controlling the motion behavior of high-towing-force catalytic micromotors.

Self-propelled micromachines for analytical sensing: a critical review.

Self-propelled micromotors are micro- and nanoscale devices that move autonomously in solution by converting a specific stimulus into mechanical work. The broad scope of operations and applications along with the ultra-small dimensions have opened new possibilities to solve complex analytical challenges. Herein we give a critical overview of early developments and future prospects of such tiny moving objects for different analytical sensing and biosensing strategies. From early electrophoretic propelled nanomotors, which were limited to low viscous media, to bubble-propelled micromotors, the field has evolved into sophisticated all-in-one analytical systems with built-in sensing capabilities. Current progress for in vivo biosensing and integration into analytical instrumentation towards fully functional devices will be also covered. We hope that this review provides the reader with some general knowledge and future prospects of self-propelled micromachines as a new paradigm in analytical chemistry. Graphical abstract.

Visible-Light-Driven Janus Microvehicles in Biological Media.

A light-driven multifunctional Janus micromotor for the removal of bacterial endotoxins and heavy metals is described. The micromotor was assembled by using the biocompatible polymer polycaprolactone for the encapsulation of CdTe or CdSe@ZnS quantum dots (QDs) as photoactive materials and an asymmetric Fe3 O4 patch for propulsion. The micromotors can be activated with visible light (470-490 nm) to propel in peroxide or glucose media by a diffusiophoretic mechanism. Efficient propulsion was observed for the first time in complex samples such as human blood serum. These properties were exploited for efficient endotoxin removal using lipopolysaccharides from Escherichia coli O111:B4 as a model toxin. The micromotors were also used for mercury removal by cationic exchange with the CdSe@ZnS core-shell QDs. Cytotoxicity assays in HeLa cell lines demonstrated the high biocompatibility of the micromotors for future detoxification applications.

Multi-Light-Responsive Quantum Dot Sensitized Hybrid Micromotors with Dual-Mode Propulsion.

CdS quantum dots/C60 tubular micromotors with chemical/multi-light-controlled propulsion and "on-the-fly" acceleration capabilities are described. In situ growth of CdS quantum dots on the outer fullerene layer imparts this layer with light-responsive properties in connection to inner Pt, Pd or MnO2 layers. This is the first time that visible light is used to drive bubble-propelled tubular micromotors. The micromotors exhibit a broad absorption range from 320 to 670 nm and can be wirelessly controlled by modulating light intensity and peroxide concentration. The built-in accelerating optical system allows for the control of the velocity over the entire UV/Vis light spectra by modulating the catalyst surface chemistry. The light-responsive properties have been also exploited to accelerate the chemical dealloying and propulsion of micromotors containing a Cu/Pd layer. Such dual operated hybrid micromotors hold considerable promise for designing smart micromachines for on-demand operations, motion-based sensing, and enhanced cargo transportation.

Self-Propelled Micromotors for Naked-Eye Detection of Phenylenediamines Isomers.

Tubular micromotors composed of a hybrid single-wall carbon nanotube (SW)-Fe2O3 outer layer and powered by a MnO2 catalyst are used for phenylenediamines isomers detection and discrimination. Catalytic decomposition of H2O2 as fuel results in the production of oxygen bubbles and hydroxyl radicals for phenylenediamines dimerization to produce colorful solutions in colorimetric assays. The combination of Fe2O3 nanoparticles along with the irregular SW backbone results in a rough catalytic layer for enhanced hydroxyl radical production rate and improved analytical sensitivity. Such self-propelled micromotors act as peroxidase-like mobile platforms that offer efficient phenylenediamines detection and discrimination in just 15 min. Factors influencing the colorimetric assay protocol, such as the navigation time and number of motors, have been investigated. Low limits of detection (5 and 6 µM) and quantification (17 and 20 µM) were obtained for o-phenylenediamine and p-phenylenediamine, respectively. The magnetic properties of the outer SW-Fe2O3 hybrid layer allow the reusability of the micromotors in the colorimetric assay. Such attractive performance holds considerable promise for its application in sensing systems in a myriad of environmental, industrial, and health applications.