resulted in a forward motion. Here, the thermodynamic forces act over the inertial thrust. Variations of this motion principle have been reported over the last decade and they will be discussed accordingly in the following sections depending on the micromotor design and the energy source used for its propulsion (i.e., concentration gradient, electric fields, magnetic fields, thermal gradients). Additionally, different approaches to improve the performance in terms of velocity, control, lifetime, and functionality will be covered. However, there are certain constraints on the synthetic autonomous nano-and microparticle performance, such as poor interaction with the surrounding environment (i.e., biological entities) and lack of sensing capabilities, in addition to low lifespan or related toxicity issues. Therefore, biohybrid particulate micromotors appear as a promising solution to overcome such hurdles. They take advantage of the tailored and advanced functions of biological cells or microorganism, such as self-propulsion, sensing, and cargo capabilities, as well as their ability to interact with other cells. Together with the controllability of engineered microobjects, hybrid micro-and nanomotors represent a promising tool for diverse biomedical and environmental applications, where the main power source comes from their natural environment. [11] As shown in Figure 1, in this review we classify micro-and nanoparticle micromotors in two main categories: synthetic and biohybrids. The synthetic micromotors are then divided according to their propulsion mechanism, as follows: those propelled by a catalytic reaction, by optical stimuli, under magnetic fields, with ultrasound steering, electricity, and thermophoresis, respectively. Likewise, the biohybrids are classified as those propelled by bacteria and those employing enzymes as main energy source, respectively. Additionally, we point out the different methods that have been proposed during the last decade to guide the particles and the related collective behavior. We also discuss the potential applications and remaining challenges in the final section of the review. Synthetic Micro/Nanoparticle MotorsThe development of the first sphere-like synthetic micro-and nanomachines with their rotationally symmetric shape was particularly challenging. As per se, they contradict the first rule in the design of microscale devices aiming to perform an effective motility in response to specific energy input: they must present asymmetry. Such symmetry breaking can be associated with shape or the distribution of a certain reactive The growing interest in the design and fabrication of novel autonomous micro-and nanoparticles is motivated by the vast advances in their motion efficiency and their further implementation in both biomedical and environmental fields. The present review covers the motion principle and fabrication procedures of synthetic and hybrid particle-like micromotors reported to date to give a comprehensive view of the key design parameters and different approaches...

We report an ultrasensitive label-free DNA biosensor with fully on-chip integrated rolled-up nanomembrane electrodes. The hybridization of complementary DNA strands (avian influenza virus subtype H1N1) is selectively detected down to attomolar concentrations, an unprecedented level for miniaturized sensors without amplification. Impedimetric DNA detection with such a rolled-up biosensor shows 4 orders of magnitude sensitivity improvement over its planar counterpart. Furthermore, it is observed that the impedance response of the proposed device is contrary to the expected behavior due to its particular geometry. To further investigate this difference, a thorough model analysis of the measured signal and the electric field calculation is performed, revealing enhanced electron hopping/tunneling along the DNA chains due to an enriched electric field inside the tube. Likewise, conformational changes of DNA might also contribute to this effect. Accordingly, these highly integrated three-dimensional sensors provide a tool to study electrical properties of DNA under versatile experimental conditions and open a new avenue for novel biosensing applications (i.e., for protein, enzyme detection, or monitoring of cell behavior under in vivo like conditions).

Due to the heterogeneity that exists even between cells of the same tissue, it is essential to use techniques and devices able to resolve the characteristics of single biological cells, such as morphology, metabolism, or response to drugs. To that end, different structures with sizes similar to that of individual cells have been developed in recent years, which allow single‐cell studies with high sensitivity and high resolution. By employing a variety of sensing strategies, one can obtain complementary information about individual cells, and thus create a complete picture of cellular properties. This review aims to provide an overview of microscale single‐cell sensors. The progress in micrometer‐sized sensing probes as well as microfluidic and micropatterned devices is described, showing the capabilities of the available systems. In addition, a comprehensive compendium of systems based on rolled‐up microtubes, which have the potential to advance and improve the single‐cell analysis microsystem field, is comprised.

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The intriguing properties of self-assembled microtubular architectures open new possibilities to develop three-dimensional functional devices for molecule and cell analysis. Here, we present an overview of novel applications ranging from highly sensitive protein detection towards cell analysis by either in-flow detection or impedimetric microtomography. The concept "lab in a tube", introduced previously by E. Smith in our institute in 2012 was presented as the integration of different components into a single microtube. It not only constitutes an interesting threedimensional platform for cell analysis, but also serves as a building block for the incorporation of sensing and actuation components. This concept is based on rolled-up nanotechnology, which consists in deposition of strained nanomembranes on a sacrificial layer that is later selectively etched, transforming a 2D architecture into a tube-like device. In our group, we have developed high-performance electrochemical sensors by integrating electrical transducers in such microtubes. The axial configuration enhances the sensing capabilities in microfluidic devices as the sensing surface per fluid volume and total capacitance increase, favoring in this way the signal coupling with the detection volume of the sample. Our reported DNA biosensor showed superior sensitivity of four orders of magnitude compared to the equivalent planar counterparts, achieving attomolar detection levels of Avian Influenza Virus H1N1 DNA, without amplification or labeling. As a follow-up application, we proposed a direct and ultrasensitive detection system of VP40 matrix protein from Ebola virus, a virus of high relevance due to its high fatality rate. In this approach, we immobilized the capture antibody in the inner part of the tube and by incubating the analyte in-flow, attomolar levels of detection were achieved with high reproducibility and repeatability. The different functionalization steps were confirmed by XPS and AFM measurements. Further electrode nanopatterning within the tubular cavity will be developed in order to increase the sensitivity of the sensor. Our second device is a rolled-up high-throughput cell detection platform, which differs from existing ones because of its particular geometry and electrode configuration that allow highly sensitive detection with a simple readout system. In this approach, multiple rolled-up electrodes within a single tube, precisely integrated in a microfluidic channel, are implemented. Finally, as a complementary technique, a tubular electrical impedance microtomography (EIT) device was fabricated. This approach gives access to EIT devices with tunable sizes in the sub-100 µm range. EIT images of silicon dioxide microparticles were obtained as proof of principle. These devices could enable the impedimetric analysis of biological samples, such as single cells or small cell clusters. In the future, measurements will be carried out to study the behavior of single cells towards external stimuli, e.g., drugs or implant materials.