Search

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.

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.

Wearable sensors for noninvasive monitoring of physiological parameters is a growing technology in the clinical field. Especially in neonates, the development of portable and nonharmful monitoring devices is urgently needed because they cannot provide any feedback about discomfort or health complaints. However, in infant monitoring, only wearable sensors measuring physical parameters for vital signs have been developed. Here, we describe the first chemical wearable sensor for newborn monitoring. This fully integrated pacifier operates as a portable wireless device toward noninvasive chemical monitoring in the infant's saliva. The infant's mouth movements on the pacifier result in efficient saliva pumping and promote unidirectional flow from the mouth to the electrochemical chamber. The integrated electrochemical detection chamber, containing the enzymatic biosensor, is located outside of the oral cavity. The capabilities of the platform were studied for glucose detection in diabetic adults and compared to their blood levels with good correlation, demonstrating the sensor's good performance. This baby-friendly device integrates saliva sampling with electrochemical sensing, along with miniaturized wireless electronics on a single pacifier platform. Such integration simplifies the infant's health monitoring in a real-time and selective fashion, representing the first wearable sensor focusing on chemical saliva sensing in newborns. This initial demonstration of glucose monitoring introduces new possibilities for metabolites monitoring in infants and neonates using saliva as a noninvasive sample.

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.

Metabolic rare diseases present a serious clinical manifestation causing several problems such as mental retardation, liver damage, hepatocarcinoma and even death without a diagnosis in the first days of life. Additionally, there is not any final treatment for these diseases but a dietary restriction, so patients have to control their biomarkers level during their whole life. Current methods for diagnosis and monitoring are tedious, very time-consuming, not portable and need high amount of sample, so they are not suitable for a point-of-care (POC) application. In this sense, electrochemistry presents the required characteristics to be used as POC for metabolic rare diseases. Specifically, this review explores the current methods for amino acids and carbohydrates sensing as biomarkers of metabolic rare diseases using electrochemical (bio)-sensing approaches, especially those based on nanomaterials in both, off and on-chip detection, as well as their suitability in metabolic rare diseases diagnosis and monitoring using clinical samples.

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.

Glycoproteins are excellent biomarkers for diagnosis and prognosis of several illnesses. α-1-Acid glycoprotein (AGP) and transferrin (Tf) are the main glycoproteins present in the serum, whose levels are increased during disease or injury. In this work, a selective detection of these glycoproteins using a microchip electrophoresis-electrochemical detection (ME-ED) platform is proposed for the first time. Because of the reduced sensitivity of glycoproteins, they were labeled with an electrochemical tag (osmium(VI) complex), which binds only to glycans, increasing the amperometric signal. Interestingly, oxidation potential of glycoprotein-Os(VI) adducts started at +0.50 V (vs Ag/AgCl) while nontagged glycoproteins started at +0.60 V. So, when the detection potential is set at +0.50 V, only glycoproteins tagged with Os(VI) complex are detected, avoiding the interference of the rest of the proteins. Determination of AGP and Tf was successfully demonstrated in the analysis of a certified human serum reference material yielding excellent accuracy (

We report on a wearable tear bioelectronic platform, integrating a microfluidic electrochemical detector into an eyeglasses nose-bridge pad, for non-invasive monitoring of key tear biomarkers. The alcohol-oxidase (AOx) biosensing fluidic system allowed real-time tear collection and direct alcohol measurements in stimulated tears, leading to the first wearable platform for tear alcohol monitoring. Placed outside the eye region this fully wearable tear-sensing platform addresses drawbacks of sensor systems involving direct contact with the eye as the contact lenses platform. Integrating the wireless electronic circuitry into the eyeglasses frame thus yielded a fully portable, convenient-to-use fashionable sensing device. The tear alcohol sensing concept was demonstrated for monitoring of alcohol intake in human subjects over multiple drinking courses, displaying good correlation to parallel BAC measurements. We also demonstrate for the first time the ability to monitor tear glucose outside the eye and the utility of wearable devices for monitoring vitamin nutrients in connection to enzymatic flow detector and rapid voltammetric scanning, respectively. These developments pave the way to build an effective eyeglasses system capable of chemical tear analysis.

Here, the on-line coupling of millimeter size motors (m-motors) and chronoamperometry for real time bio-sensing of branched-chain amino acids ( l -b-AAs) in maple syrup urine disease (MSUD) clinical samples is proposed. Marangoni effect for controlled mixing and delivery of active enzyme for substrate digestion and subsequent electrochemical sensing is conveniently explored. To this end, an integrated cell device, which includes reservoirs for motors movement and electrochemical detection, was fabricated. l -amino acid oxidase (LAO)-loaded m-motors just by capillarity without any coating chemistry are used for the enantiomers selective recognition, and then the hydrogen peroxide released from enzymatic reaction is electrochemically monitored at −0.20 V using copper microwires as exclusive transducers. The inherent enzyme m-motor features – “self-micro mixing” and the continuous release of fresh and free enzyme-, not only avoided the use of external stirring or the enzymatic physical adsorption or chemical bonding to the electrode; but a dramatic decreasing of analysis times (just 200 s vs. 25 min without motors, yielding only a 70% of the m-motor signal). In addition, an excellent accuracy (Er l -b-AAs determination in clinical samples from patients previously diagnosed by a reference center was also obtained. We envision future opportunities for this approach to be a potential point of care (POC) testing device, because of its rapid response, simplicity, selectivity and sensitivity; becoming into another step facing towards the challenges of rare disease diagnostics.

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.

Introduction Uveal melanoma is a rare tumour caused by genetic factors and alterations in the immune response. Inflammatory bowel disease (IBD) is a multifactorial chronic inflammatory disorder characterized by an inappropriate or excessive immune response. The two main types of IBD are Crohn's disease (CD) and ulcerative colitis (UC). A diagnosis of IBD and the use of immunosuppressive drugs are both independently associated with an increased risk of developing skin melanoma. The association between IBD and uveal melanoma (UM) has not been previously described. Cases description Two young Caucasian men, aged 24 and 28, developed UM 3 and 15 years, respectively, after being diagnosed with IBD. Both received long-term treatment with immunomodulatory drugs, with periodic switching among the drugs due to the refractory nature of IBD. In both cases, melanoma was treated by brachytherapy with iodine-125 COMS plaque implant at a dose of 75 Gy. Discussion Chronic inflammation can promote cell proliferation and growth. The use of immunomodulatory drugs is associated with an increased risk of developing melanoma and non-melanoma skin cancer. The two patients described in this report both had long-standing IBD treated with immunomodulatory drugs. It seems reasonable to suggest that these two factors may have promoted the development of uveal melanoma. More studies are warranted to investigate and confirm this possible association.

Janus micromotors are a unique class of materials whose surfaces have two or more distinct physical properties, allowing thus for two types of chemistry to occur simultaneously. Judicious design of the micromotor structure allows to incorporate different functionalities in a single unit to adapt the propulsion behaviour along with the incorporation of specific receptors for a myriad of applications. Herein we report the preparation of graphene oxide (GO)/PtNPs/Fe2O3 Janus micromotors for highly selective capture/inactivation of gram-positive bacteria units and biofilms. The strategy is based on the combination of a lanbiotic (Nisin) with Janus micromotors. Lanbiotics are peptides composed of methyllanthionine residues with a highly selective antimicrobial activity towards multidrug resistant bacteria. Nisin is a natural compound normally used for food preservation, which display specific antimicrobial activity towards gram-positive bacteria. Such peptide can bind to lipid II unit of the bacteria membranes, damaging its morphology and releasing its contents. The coating of micromotors with GO impart them with a Janus structure for the subsequent asymmetric assembly of catalytic (PtNPs) and magnetic (Fe2O3) engines and results in an active rough layer for a higher loading of Nisin via covalent interactions. The micromotors possess adaptative propulsion mechanisms, including catalytic mode (PtNPs) in peroxide solutions or magnetic actuation (fuel free) by the action of an external magnetic field. The enhanced movement and localized delivery of the micromotors (both in catalytic and magnetic actuated mode) results in a 2-fold increase of the capture/killing ability towards Staphylococcus Aureus bacteria in raw media (juice, serum and tap water samples), as compared with free Nisin and static counterparts. The micromotor strategy display also high selectivity towards such bacteria, as illustrated by the dramatically lower capture/killing ability towards gram-negative Escherichia Coli. Unlike previous micromotors based strategies, this approach displays higher selectivity towards a type of bacteria along with enhanced stability, prolonged use and adaptative propulsion modes, holding considerable promise to treat methicillin resistant antibiotic infections, for environmental remediation or food safety, among others applications.

Mi investigación gira en torno a la imagen autorrepresentativa en la cultura web y las relaciones que establecemos con y mediante ésta. Cuestiono cómo la tecnología impacta en nuestra cotidianidad y espacios de intimidad, convirtiéndolos en mercancía del espectáculo, al tiempo que fomenta relaciones de control, vigilancia y alienación. En la esencia de todo mi trabajo está la desconfianza hacia las imágenes, la sospecha hacia nuestra cultura y la duda sobre en qué medida somos víctimas o responsables de todo esto. Para ello, hago uso de diversas disciplinas como la fotografía, el vídeo, la performance, el happening o la escultura, con las que trato de utilizar elementos y materiales cotidianos, en una práctica fundamentada en el proceso plástico-conceptual, antes que en la consecución de resultados. Como consecuencia de este proceso experimental en el taller, las obras adquieren formatos y lenguajes diversos, aunque surgen de los mismos intereses y dinámicas, por lo que pueden mostrarse de forma independiente o en conjunto.

A new family of polyphenolic carbosilane dendrimers functionalized with ferulic, caffeic, and gallic acids has been obtained through a straightforward amidation reaction. Their antioxidant activity has been studied by different techniques such as DPPH (2,2'-diphenyl-1-picrylhydrazyl) radical scavenging assay, FRAP assay (ferric reducing antioxidant power), and cyclic voltammetry. The antioxidant analysis showed that polyphenolic dendrimers exhibited higher activities than free polyphenols in all cases. The first-generation dendrimer decorated with gallic acid stood out as the best antioxidant compound, displaying a correlation between the number of hydroxyl groups in the polyphenol structure and the antioxidant activity of the compounds. Moreover, the antibacterial capacity of these new systems has been screened against Gram-positive (+) and Gram-negative (-) bacteria, and we observed that polyphenolic dendrimers functionalized with caffeic and gallic acids were capable of decreasing bacterial growth. In contrast, ferulic carbosilane dendrimers and free polyphenols showed no effect, establishing a correlation between antioxidant activity and antibacterial capacity. Finally, a viability assay in human skin fibroblasts cells (HFF-1) allowed for corroborating the nontoxicity of the polyphenolic dendrimers at their active antibacterial concentration.

Background Organ and tissue recovery remains limited by several factors. This study retrospectively analyzes the factors associated with family refusal to consent to donation at a high-donor-volume Spanish hospital. Methods Data regarding the annual number of potential donors and family refusal rates at hospital and regional levels were retrieved from 2008 to 2017. Descriptive, bivariate, and multivariate analyses were performed to detect those factors independently associated with family refusal. Results were cross-validated using the data from years 2018 and 2019 as the validation group. To explore potential inter-relations between factors a Multiple Correspondence Analysis was performed. Results A total of 601 family interviews for petition of consent were conducted between 2008 and 2017, 531 (88.4%) resulted in acceptance and 70 (11.6%) resulted in refusal of the donation. Lesser experience of the interviewers (odds ratio [OR], 2.980; P = .001), donation after brain death (OR, 2.485; P = .013), number of interviews conducted per family (OR, 1.892; P < .001), age of the main decision maker (OR, 1.025; P = .045), and high or middle attributed cultural levels (OR, 0.142; P < .001 and OR, 0.199; P < .001 respectively) were observed to be independently associated with the family final decision. The logistic regression model displayed good predictive power for both derivation and validation cohorts, with an overall predictive accuracy of 80.9% (95% confidence interval, 0.747-0.870; P < .001) and 74.4% (95% confidence interval, 0.635-0.854; P = .001), respectively. Conclusions Transplant coordination team members having a thorough knowledge of the family decision mechanisms may be a key factor in donation process optimization. post-print 633 KB

In this book chapter, the advances in the determination of carbohydrates and glycoconjugates by capillary and microchip electrophoresis with electrochemical detection (CE/ME-ED) will be studied, covering from 2002 to 2019. Amperometric detection, capacitively coupled contactless conductivity detection, and enzyme-based amperometric detection as well as electrochemical derivatization schemes will be critically discussed, showing their advantages and limitations. Furthermore, the most important applications in clinical, pharmaceutical, and food fields will also be highlighted. Future outlooks of CE/ME-ED for carbohydrate determination will also be shown, pointing out those strategies that may improve the sensitivity and selectivity of analytical methods.

Carbohydrate deficient transferrin (CDT) is used as biomarker of different health problems as, for example, congenital disorders of glycosylation (CDG). We propose a screen-printed-based electrochemical sensor for the determination of carbohydrate deficient transferrin using an Os (VI) tag-based electrochemistry. When transferrin is labeled with Os (VI) complex, it generates two voltammetric signals: one from carbohydrates (electrochemical signal of osmium (VI) complex at -0.9 V/Ag) and one from the amino acids present in glycoprotein (intrinsic electrochemical signal of glycoprotein at +0.8 V/Ag). The relationship between the two analytical signals (carbohydrate signal/protein signal) is an indicator of the degree of glycosylation (electrochemical index of glycosylation), which has shown an excellent correlation (r = 0.990) with the official parameter %CDT obtained by CE-UV. The suitability of this approach was demonstrated by analyzing serum samples from CDG patients.

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.

Graphene oxide/PtNPs/Fe2O3"dual-propelled" catalytic and fuel-free rotary actuated magnetic Janus micromotors modified with the antimicrobial peptide 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 results 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 micromotor 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.

A Prussian blue-based electrode array (PBEA) constituted by eight stencil-printed electrodes on a flexible PET (polyethylene terephthalate) substrate is proposed for in-situ HeLa cell culturing and real-time detection of the released H

A new family of polyphenolic carbosilane dendrimers functionalized with ferulic, caffeic, and gallic acids has been obtained through a straightforward amidation reaction. Their antioxidant activity has been studied by different techniques such as DPPH (2,2 '-diphenyl-1-picrylhydrazyl) radical scavenging assay, FRAP assay (ferric reducing antioxidant power), and cyclic voltammetry. The antioxidant analysis showed that polyphenolic dendrimers exhibited higher activities than free polyphenols in all cases. The first-generation dendrimer decorated with gallic acid stood out as the best antioxidant compound, displaying a correlation between the number of hydroxyl groups in the polyphenol structure and the antioxidant activity of the compounds. Moreover, the antibacterial capacity of these new systems has been screened against Gram-positive (+) and Gram-negative (-) bacteria, and we observed that polyphenolic dendrimers functionalized with caffeic and gallic acids were capable of decreasing bacterial growth. In contrast, ferulic carbosilane dendrimers and free polyphenols showed no effect, establishing a correlation between antioxidant activity and antibacterial capacity. Finally, a viability assay in human skin fibroblasts cells (HFF-1) allowed for corroborating the nontoxicity of the polyphenolic dendrimers at their active antibacterial concentration., Ministerio de Economía y Competitividad, Junta de Comunidades de Castilla-La Mancha, Comunidad de Madrid

A novel on-chip electrochemical magneto-immunoassay for the determination of procalcitonin (PCT) has been proposed. The strategy involved the on-line performing of the biorecognition event and detection on the thin-film microfluidic gold electrode chamber operating at E = -0.20 V (vs. Au). The complete assay was performed in less than 15 minutes using only 25 μL of the sample, covering the entire range of clinically relevant PCT concentrations in sepsis diagnosis with a limit of detection and quantification of 0.02 ng mL-1 and 0.05 ng mL-1, respectively (the sepsis diagnosis threshold: 0.5 ng mL-1). The on-chip electrochemical magneto-immunoassay provided excellent results in the analysis of very unique samples obtained from preterm neonates admitted with suspected sepsis, in which the sample volume is hardly available. These characteristics fulfill the POCT requirements for PCT determination in the whole clinically relevant concentration range. Because of the high clinical relevance and the important role of PCT in sepsis, this approach opens new perspectives for sepsis diagnosis and therapy guidance using low volume samples.

Procalcitonin (PCT) is a known protein biomarker clinically used for the early stages of sepsis diagnosis and therapy guidance. For its reliable determination, sandwich format magnetic bead-based immunoassays with two different electrochemical detection approaches are described: (i) disposable screen-printed carbon electrodes (SPE-C, on-drop detection), (ii) electro-kinetically driven microfluidic chips with integrated Au electrodes (EMC-Au, on-chip detection). Both approaches exhibited enough sensitivity (limit of detection (LOD) of 0.1 and 0.04 ng mL&minus, 1 for SPE-C and EMC-Au, respectively, cutoff 0.5 ng mL&minus, 1), an adequate working range for the clinically relevant concentrations (0.5&ndash, 1000 and 0.1&ndash, 20 ng mL&minus, 1 for SPE-C and EMC-Au, respectively), and good precision (RSD &lt, 9%), using low sample volumes (25 &micro, L) with total assay times less than 20 min. The suitability of both approaches was successfully demonstrated by the analysis of human serum and plasma samples, for which good recoveries were obtained (89&ndash, 120%). Furthermore, the EMC-Au approach enabled the easy automation of the process, constituting a reliable alternative diagnostic tool for on-site/bed-site clinical analysis.

Herein we describe an "OFF-ON" Janus micromotor approach for the fast (5 min) and sensitive determination (limit of detection, 120 pM) of Escherichia coli O111:B4 lipopolysaccharide (LPS) associated with sepsis shock in microliter samples. The OFF-ON strategy relies on the loading of a specifically designed rhodamine-labeled affinity peptide into WS

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.