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The central nervous system (CNS) is protected by the blood-brain barrier (BBB), which acts as a physical barrier to regulate and prevent the uptake of endogenous metabolites and xenobiotics. However, the BBB prevents most non-lipophilic drugs from reaching the CNS following systematic administration. Therefore, there is considerable interest in identifying drug carriers that can maintain the biostability of therapeutic molecules and target their transport across the BBB. In this regard, upconversion nanoparticles (UCNPs) have become popular as a nanoparticle-based solution to this problem, with the additional benefit that they display unique properties for in vivo visualization. The majority of studies to date have explored basic spherical UCNPs for drug delivery applications. However, the biophysical properties of UCNPs, cell uptake and BBB transport have not been thoroughly investigated. In this study, we described a one-pot seed-mediated approach to precisely control longitudinal growth to produce bright UCNPs with various aspect ratios. We have systematically evaluated the effects of the physical aspect ratios and PEGylation of UCNPs on cellular uptake in different cell lines and an in vivo zebrafish model. We found that PEGylated the original UCNPs can enhance their biostability and cell uptake capacity. We identify an optimal aspect ratio for UCNP uptake into several different types of cultured cells, finding that this is generally in the ratio of 2 (length/width). This data provides a crucial clue for further optimizing UCNPs as a drug carrier to deliver therapeutic agents into the CNS. STATEMENT OF SIGNIFICANCE: The central nervous system (CNS) is protected by the blood-brain barrier (BBB), which acts as a highly selective semipermeable barrier of endothelial cells to regulate and prevent the uptake of toxins and pathogens. However, the BBB prevents most non-lipophilic drugs from reaching the CNS following systematic administration. The proposed research is significant because identifying the aspect ratio of drug carriers that maintains the biostability of therapeutic molecules and targets their transport across the blood-brain barrier (BBB) is crucial for designing an efficient drug delivery system. Therefore, this research provides a vital clue for further optimizing UCNPs as drug carriers to deliver therapeutic molecules into the brain.

Upconversion nanoparticles are a class of luminescent materials that convert longer-wavelength near-infrared photons into visible and ultraviolet emissions. They can respond to various external stimuli, which underpins many opportunities for developing the next generation of sensing technologies. In this perspective, the unique stimuli-responsive properties of upconverting nanoparticles are introduced, and their recent implementations in sensing are summarized. Promising material development strategies for enhancing the key sensing merits, including intrinsic sensitivity, biocompatibility and modality, are identified and discussed. The outlooks on future technological developments, novel sensing concepts, and applications of nanoscale upconversion sensors are provided.

Microrobots can expand our abilities to access remote, confined, and enclosed spaces. Their potential applications inside our body are obvious, e.g., to diagnose diseases, deliver medicine, and monitor treatment efficacy. However, critical requirements exist in relation to their operations in gastrointestinal environments, including resistance to strong gastric acid, responsivity to a narrow proton variation window, and locomotion in confined cavities with hierarchical terrains. Here, we report a proton-activatable microrobot to enable real-time, repeated, and site-selective pH sensing and monitoring in physiological relevant environments. This is achieved by stratifying a hydrogel disk to combine a range of functional nanomaterials, including proton-responsive molecular switches, upconversion nanoparticles, and near-infrared (NIR) emitters. By leveraging the 3D magnetic gradient fields and the anisotropic composition, the microrobot can be steered to locomote as a gyrating "Euler's disk", i.e., aslant relative to the surface and along its low-friction outer circumference, exhibiting a high motility of up to 60 body lengths/s. The enhanced magnetomotility can boost the pH-sensing kinetics by 2-fold. The fluorescence of the molecular switch can respond to pH variations with over 600-fold enhancement when the pH decreases from 8 to 1, and the integration of upconversion nanoparticles further allows both the efficient sensitization of NIR light through deep tissue and energy transfer to activate the pH probes. Moreover, the embedded down-shifting NIR emitters provide sufficient contrast for imaging of a single microrobot inside a live mouse. This work suggests great potential in developing multifunctional microrobots to perform generic site-selective tasks in vivo.

Cancer-derived small extracellular vesicles (sEVs) are potential circulating biomarkers in liquid biopsies. However, their small sizes, low abundance, and heterogeneity in molecular makeups pose major technical challenges for detecting and characterizing them quantitatively. Here, we demonstrate a single-sEV enumeration platform using lanthanide-doped upconversion nanoparticles (UCNPs). Taking advantage of the unique optical properties of UCNPs and the background-eliminating property of total internal reflection fluorescence (TIRF) imaging technique, a single-sEV assay recorded a limit of detection 1.8 × 106 EVs/mL, which was nearly 3 orders of magnitude lower than the standard enzyme-linked immunosorbent assay (ELISA). Its specificity was validated by the difference between EpCAM-positive and EpCAM-negative sEVs. The accuracy of the UCNP-based single-sEV assay was benchmarked with immunomagnetic-beads flow cytometry, showing a high correlation (R2> 0.99). The platform is suitable for evaluating the heterogeneous antigen expression of sEV and can be easily adapted for biomarker discoveries and disease diagnosis.

Polymer microspheres can be fluorescently-coded for multiplexing molecular analysis, but their usage has been limited by fluorescent quenching and bleaching and crowded spectral domain with issues of cross-talks and background interference. Each bioassay step of mixing and separation of analytes and reagents require off-line particle handling procedures. Here, we report that stray magnetic fields can code and decode a collection of hierarchically-assembled beads. By the microfluidic assembling of mesoscopic superparamagnetic cores, diverse and non-volatile stray magnetic field response can be built in the series of microscopic spheres, dumbbells, pears, chains and triangles. Remarkably, the set of stray magnetic field fingerprints are readily discerned by a compact giant magnetoresistance sensor for parallelised screening of multiple distinctive pathogenic DNAs. This opens up the magneto-multiplexing opportunity and could enable streamlined assays to incorporate magneto-mixing, washing, enrichment and separation of analytes. This strategy therefore suggests a potential point-of-care testing solution for efficient kinetic assays.

Microrobots can expand our abilities to access remote, confined, and enclosed spaces. Their potential applications inside our body are obvious

Peristalsis in the digestive tract is crucial to maintain physiological functions. It remains challenging to mimic the peristaltic microenvironment in gastrointestinal organoid culture. Here, we present a method to model the peristalsis for human colon tumor organoids on a microfluidic chip. The chip contains hundreds of lateral microwells and a surrounding pressure channel. Human colon tumor organoids growing in the microwell were cyclically contracted by pressure channel, mimicking the in vivo mechano-stimulus by intestinal muscles. The chip allows the control of peristalsis amplitude and rhythm and the high throughput culture of organoids simultaneously. By applying 8% amplitude with 8 ∼ 10 times min−1, we observed the enhanced expression of Lgr5 and Ki67. Moreover, ellipticine-loaded polymeric micelles showed reduced uptake in the organoids under peristalsis and resulted in compromised anti-tumor efficacy. The results indicate the importance of mechanical stimuli mimicking the physiological environment when using in vitro models to evaluate nanoparticles. This work provides a method for attaining more reliable and representative organoids models in nanomedicine.

Magnetic tweezers are crucial for single-molecule and atomic characterization, and biomedical isolation of microparticle carriers. The trapping component of magnetic tweezing can be relying on a magnetic potential well that can confine the relevant species to a localized region. Here, we report that magnetic microparticles with tailored anisotropy can transition from localized off-axis gyration to large-area locomotion in a rotating magnetic trap. The microparticles, consisting of assemblies of magnetic cores, are observed to either rotate about its structural geometric center or gyrate about one of the magnetic cores, the switching of which can be modulated by the external field. Raising the magnetic field strength above a threshold, the particles can go beyond the traditional synchronous-rotation and asynchronous-oscillation modes, and into a scenario of large-area circular motion. This results in peculiar retrograde locomotion related to the magnetization maxima of the microparticle. Our finding suggests the important role of the microparticle's magnetic morphology in the controlled transport of microparticles and developing smart micro-actuators and micro-robot devices., Comment: 4 figures

Thermally responsive fluorescent nanoparticles can be constructed to allow robust, rapid, and noninvasive temperature measurements. Furthermore, due to their tiny size, they can be used to detect t...

Magnetic microrobots with versatile mechanical motion will enable many ex- and in vivo applications. Unfortunately, monolithic integration of multiple functions in a streamlined microrobotic body is still challenging due to the compromise between fabrication throughput, device footprints, and material choices. In this talk, I will present a unified framework architecture for microrobotic functionalization to enable magnetically steered locomotion, chemical sensing and in vivo tracking. This has been achieved through stratifying stimuli-responsive nanoparticles in a hydrogelmicro-disk. We uncovered the key mechanism of leveraging spatially alternating magnetic energy potential to control a Euler’s disk-like microrobot to locomote swiftly on its sidewall. The results suggest great potential for microrobots to locomote while cooperating a wide range of functions, tailorable for universal application scenarios.

Utilizing the magnetic interactions between microparticle building blocks allows creating long‐range ordered structures and constructing smart multifunctional systems at different scales. The elaborate control over the inter‐particle magnetic coupling interaction is entailed to unlock new magnetoactuation functionalities. Herein, dimer‐type microstructures consisting of a pair of magnetic emulsions with tailorable dimension and magnetic coupling strength are fabricated using a microfluidic emulsion‐templated assembly approach. The magnetite nanoparticles dispersed in vinylbenzene monomers are partitioned into a pair of emulsions with conserved volume, which are wrapped by an aqueous hydrogel shell and finally polymerized to form discrete structures. Tunable synchronous–asynchronous rotation over 60 dB is unlocked in magnetic dimers, which is shown to be dependent on the magnetic moments induced. This leads to a new class of magnetic actuators for the parallelized assay of distinctive virus DNAs and the dynamic optical evaluation of 3D cell cultures. The work suggests a new perspective to design smart multifunctional microstructures and devices by exploring their natural variance in magnetic coupling.

Precise design and fabrication of heterogeneous nanostructures will enable nanoscale devices to integrate multiple desirable functionalities. But due to the diffraction limit (~200 nm), the optical uniformity and diversity within the heterogeneous functional nanostructures are hardly controlled and characterized. Here, we report a set of heterogeneous nanorods; each optically active section has its unique nonlinear response to donut-shaped illumination, so that one can discern each section with super-resolution. To achieve this, we first realize an approach of highly controlled epitaxial growth and produce a range of heterogeneous structures. Each section along the nanorod structure displays tunable upconversion emissions, in four optical dimensions, including color, lifetime, excitation wavelength, and power dependency. Moreover, we demonstrate a 210 nm single nanorod as an extremely small polychromatic light source for the on-demand generation of RGB photonic emissions. This work benchmarks our ability toward the full control of sub-diffraction-limit optical diversities of single heterogeneous nanoparticles., Development of functional nanostructures can enable a range of applications in imaging and nanoscale science. Here, the authors fabricate and characterize complex heterogeneous nanorods with diverse, tunable sub-wavelength structures.

Precise design and fabrication of heterogeneous nanostructures will enable nanoscale devices to integrate multiple desirable functionalities. But due to the diffraction limit (~200 nm), the optical uniformity and diversity within the heterogeneous functional nanostructures are hardly controlled and characterized. Here we report a set of nanobarcodes, each optically active section has its unique nonlinear responses to donut illumination patterns, so that one can discern each unit with super resolution. To achieve this, we first realized an approach of highly controlled epitaxial growth and produced a range of one-dimensional heterogeneous structures. Each section along the nanorod structure display tunable upconversion emissions, in four optically orthogonal dimensions, including colour, lifetime, excitation wavelength, and power dependency. Moreover, we demonstrated a 210 nm single nanorod as the smallest polychromatic light source for the on-demand generation of RGB photonic emissions. Remarkably, within a space of 50 nm, only 1/20th of the excitation wavelength, multiple codes can be successfully coded and decoded in 4 optical dimensions. This precision control enables the fabrication of super capacity geometrical barcodes with theoretical coding capacity up to (24-1)4. This work benchmarks our new ability towards the full control of sub-diffraction-limit optical diversities of single heterogeneous nanoparticles.

© 2018 American Chemical Society. Paper-based lateral flow assays, though being low-cost and widely used for rapid in vitro diagnostics, are indicative and do not provide sufficient sensitivity for the detection and quantification of low abundant biomarkers for early stage cancer diagnosis. Here, we design a compact device to create a focused illumination spot with high irradiance, which activates a range of highly doped 50 nm upconversion nanoparticles (UCNPs) to produce orders of magnitude brighter emissions. The device employs a very low-cost laser diode, simplified excitation, and collection optics and permits a mobile phone camera to record the results. Using highly erbium ion (Er 3+ )-doped and thulium ion (Tm 3+ )-doped UCNPs as two independent reporters on two-color lateral flow strips, new records of limit of detection (LOD), 89 and 400 pg/mL, have been achieved for the ultrasensitive detection of prostate specific antigen (PSA) and ephrin type-A receptor 2 (EphA2) biomarkers, respectively, without crosstalk. The technique and device presented in this work suggests a broad scope of low-cost, rapid, and quantitative lateral flow assays in early detection of bioanalytes.

© 2017 American Chemical Society. Droplet-based high throughput biomolecular screening and combinatorial synthesis entail a viable indexing strategy to be developed for the identification of each microreactor. Here, we propose a novel indexing scheme based on the generation of droplet sequences on demand to form unique encoding droplet chains in fluidic networks. These codes are represented by multiunit and multilevel droplets packages, with each code unit possessing several distinct signal levels, potentially allowing large encoding capacity. For proof of concept, we use magnetic nanoparticles as the encoding material and a giant magnetoresistance (GMR) sensor-based active sorting system supplemented with an optical detector to generate and decode the sequence of one exemplar sample droplet reactor and a 4-unit quaternary magnetic code. The indexing capacity offered by 4-unit multilevel codes with this indexing strategy is estimated to exceed 104, which holds great promise for large-scale droplet-based screening and synthesis.

Mammary tumor organoids have become a promising in vitro model for drug screening and personalized medicine. However, the dependency on the basement membrane extract (BME) as the growth matrices limits their comprehensive application. In this work, mouse mammary tumor organoids are established by encapsulating tumor pieces in non‐adhesive alginate. High‐throughput generation of organoids in alginate microbeads is achieved utilizing microfluidic droplet technology. Tumor pieces within the alginate microbeads developed both luminal‐ and solid‐like structures and displayed a high similarity to the original fresh tumor in cellular phenotypes and lineages. The mechanical forces of the luminal organoids in the alginate capsules are analyzed with the theory of the thick‐wall pressure vessel (TWPV) model. The luminal pressure of the organoids increase with the lumen growth and can reach 2 kPa after two weeks’ culture. Finally, the mammary tumor organoids are treated with doxorubicin and latrunculin A to evaluate their application as a drug screening platform. It is found that the drug response is related to the luminal size and pressures of organoids. This high‐throughput culture for mammary tumor organoids may present a promising tool for preclinical drug target validation and personalized medicine., Mammary tumor organoids culture heavily relies on basement membrane extract hydrogels. Herein, non‐adhesive alginate is found to be a good candidate for the culture of mouse mammary tumor organoids. Alginate microbeads generated by microfluidic droplet technique enhance the organoid's yield and are further used for luminal mechanics and high‐throughput drug screening.

© 2018 The Publisher. Stable, sharp-bandwidth and upconverted stimulated emissions are generated from a 5-μm polystyrene cavity pumped by a low-power continuous-wave excitation.

Multicellular tumor spheroids are attracting more attention as a physiologically relevant in vitro tumor model for biomedical research. The size of spheroids is one of the critical parameters related to drug penetration and cellular responses. It remains challenging to generate a large number of gradient-sized spheroids in one culture vessel. Here, a liquid-dome method was used to simultaneously produce more than 200 gradient-sized spheroids on an agarose chip. Surface tension effect was used to modulate the liquid spatial distribution and achieve a range of spheroid sizes. MCF-7 cells formed multiple spheroids on the chips for concept validation. It showed that different configurations of the liquid domes exhibited different levels of size control. Relative to the smallest spheroids in the configuration, hemispheric and square domes produced spheroids up to 3.4 and 12.8-fold larger in area, respectively. In addition, the co-culture of MCF-7 and fibroblasts helped to elucidate the tendency of fibroblasts towards the spheroid center. Other size-dependent behaviors were profiled; larger spheroids behaved differently from smaller spheroids in terms of spheroid growth, drug penetration and cellular responses. This method breaks the boundary between the preparation of gradient-sized spheroids and significant time/labour demand. It can be useful for drug screening and in vitro tumor modelling.

Cell co-culture serves as a standard method to study intercellular communication. However, random diffusion of signal molecules during co-culture may arouse crosstalk among different types of cells and hide directive signal-target responses. Here, a microfluidic chip is proposed to study unidirectional intercellular communication by spatially controlling the flow of the signal molecules. The chip contains two separated chambers connected by two channels where the culture media flows oppositely. A zigzag signal-blocking channel is designed to study the function of a specific signal. The chip is applied to study the unidirectional communication between tumor cells and stromal cells. It shows that the expression of α-smooth muscle actin (a marker of cancer-associated fibroblast (CAF)) of both MRC-5 fibroblasts and mesenchymal stem cells can be up-regulated only by the secreta from invasive MDA-MB-231 cells, but not from non-invasive MCF-7 cells. The proliferation of the tumor cells can be improved by the stromal cells. Moreover, transforming growth factor beta 1 is found as one of the main factors for CAF transformation via the signal-blocking function. The chip achieves unidirectional cell communication along X-axis, signal concentration gradient along Y-axis and 3D cell culture along Z-axis, which provides a useful tool for cell communication studies.

Coordination chemistry has been widely studied in lanthanide complexes, where organic ligands are used to chelate individual lanthanide ions, and the complexes are broadly used in analytical, biological, and clinical applications. Significant progress has recently been made to exploit the hybrid structure of lanthanide doped inorganic nanoparticles “coated” with organic dyes. This attributes to the fast developments of nanoscience and technology centred around well-controlled nanocrystal synthesis and engineering, with a variety of shape, size, composition and structures towards the desirable functions. There are a lot of similarities between the two forms of lanthanide materials, waiting for a systematic analysis to guide the emerging field of nanocrystal-dye hybrids. Therefore, we survey here the principles for the design of dye-lanthanide energy transfer systems and analyse the remarkable successes made in hybrid dye-lanthanide nanosystems.

© The Royal Society of Chemistry 2018. We report a facile approach of using DNA molecules as switches to selectively activate silica coating onto specific facets of upconversion nanoparticles. Being simple and reproducible, this method improves the understanding of the silica coating mechanism and opens up new opportunities for nanomedicine delivery.

© 2018 Elsevier Inc. Optical multiplexing has significantly boosted our capacity to acquire and process information in the modern era. This review surveys new methods for coding optical information to move from the macroscopic to the nanoscale. We highlight that advances in new materials, fabrication methods, super-resolution imaging tools, and microfluidic devices are the enabling technologies for many recent breakthroughs in micro- and nanoscale biophotonics. Multidimensional optical coding has been developed to assign addressable molecular probes for multiplexed molecular and cellular sensing. While illustrating the principles of coding information in multiple dimensions, we discuss prospective opportunities in material design and technological advancement and identify the challenges for eventually integrating and translating these biophotonic tools into cellular insights. Recent discoveries in luminescent materials, the advent of lasers, and high-resolution microscopy offer improvements to bio-discovery processes and better reporting that will ultimately boost healthcare efficiency. However, slow analysis of the screening process has limited the delivery of improved patient care. Analysis of one or two molecular or cellular targets is no longer sufficient for characterizing a disease or biochemical process, and cellular imaging typically generates significant amounts of information from even a single cell, let alone larger interacting biological systems. By developing optical multiplexing into multiple dimensions, we can significantly increase the throughput of imaging, allowing simultaneous tracking of multiple targets. The eventual goal of optical multiplexing is to synchronize developments in materials and platforms to boost the throughput of bio-discovery to enable us to mine the enormous amounts of information buried inside living organisms. Analysis of one or two molecular or cellular targets is no longer sufficient for characterizing a disease or biochemical process. Cellular imaging typically generates significant amounts of information from even a single cell, let alone larger interacting biological systems. We review new methods for coding optical information, moving from the macroscopic to the nanoscale, and discuss potential opportunities and challenges for developing optical multiplexing to boost the capacity of bio-discovery.

© 2018 American Chemical Society. Upconversion nanoparticles (UCNPs) are new optical probes for biological applications. For specific biomolecular recognition to be realized for diagnosis and imaging, the key lies in developing a stable and easy-to-use bioconjugation method for antibody modification. Current methods are not yet satisfactory regarding conjugation time, stability, and binding efficiency. Here, we report a facile and high-yield approach based on a bispecific antibody (BsAb) free of chemical reaction steps. One end of the BsAb is designed to recognize methoxy polyethylene glycol-coated UCNPs, and the other end of the BsAb is designed to recognize the cancer antigen biomarker. Through simple vortexing, BsAb-UCNP nanoprobes form within 30 min and show higher (up to 54%) association to the target than that of the traditional UCNP nanoprobes in the ELISA-like assay. We further demonstrate its successful binding to the cancer cells with high efficiency and specificity for background-free fluorescence imaging under near-infrared excitation. This method suggests a general approach broadly suitable for functionalizing a range of nanoparticles to specifically target biomolecules.

We apply the technique of supervised discriminant analysis (SDA) for in-flow detection in droplet-based magnetofluidics. Based on the SDA, we successfully discriminate bivariant droplets of different volumes containing different encapsulated magnetic content produced by a GMR-based lab-on-chip platform. We demonstrate that the accuracy of discrimination is superior when the correlation of variables for data training is included to the case when the spatial distribution of variables is considered. Droplets produced with differences in ferrofluid concentration of 2.5 mg/ml and volume of 200 pl have been identified with high accuracy (98 %), indicating the significance of SDA for e.g. the discrimination in magnetic immuno-agglutination assays. Furthermore, the results open the way for the development of a unique magnetofluidic platform for future applications in multiplexed droplet-based barcoding assays and screening. Electronic supplementary material The online version of this article (doi:10.1007/s10404-015-1579-z) contains supplementary material, which is available to authorized users.

© 2017 The Royal Society of Chemistry. Detection and quantification of a variety of micro- and nanoscale entities, e.g. molecules, cells, and particles, are crucial components of modern biomedical research, in which biosensing platform technologies play a vital role. Confronted with the drastic global demographic changes, future biomedical research entails continuous development of new-generation biosensing platforms targeting even lower costs, more compactness, and higher throughput, sensitivity and selectivity. Among a wide choice of fundamental biosensing principles, magnetic sensing technologies enabled by magnetic field sensors and magnetic particles offer attractive advantages. The key features of a magnetic sensing format include the use of commercially available magnetic field sensing elements, e.g. magnetoresistive sensors which bear huge potential for compact integration, a magnetic field sensing mechanism which is free from interference by complex biomedical samples, and an additional degree of freedom for the on-chip handling of biochemical species rendered by magnetic labels. In this review, we highlight the historical basis, routes, recent advances and applications of magnetic biosensing platform technologies based on magnetoresistive sensors.

A lab-on-chip device is demonstrated for probing the electrochemical kinetics, electrical properties, and structure integrity of a single Si rolled-up tube as the anode in lithium-ion batteries. Cyclic voltammetry of the tube exhibits better-resolved peaks than of the planar film due to the enhanced diffusion. The tube is wrinkled after cycling. The tube could be used as a promising ultra-microelectrode for other voltammetry research.

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim A novel realization of microtubular direct methanol fuel cells (µDMFC) with ultrahigh power output is reported by using “rolled-up” nanotechnology. The microtube (Pt-RuO2-RUMT) is prepared by rolling up Ru2O layers coated with magnetron-sputtered Pt nanoparticles (cat-NPs). The µDMFC is fabricated by embedding the tube in a fluidic cell. The footprint of per tube is as small as 1.5 × 10−4 cm2. A power density of ≈257 mW cm−2 is obtained, which is three orders of magnitude higher than the present microsized DFMCs. Atomic layer deposition technique is applied to alleviate the methanol crossover as well as improve stability of the tube, sustaining electrolyte flow for days. A laminar flow driven mechanism is proposed, and the kinetics of the fuel oxidation depends on a linear-diffusion-controlled process. The electrocatalytic performance on anode and cathode is studied by scanning both sides of the tube wall as an ex situ working electrode, respectively. This prototype µDFMC is extremely interesting for integration with micro- and nanoelectronics systems.

Information tagging and processing are vital in information-intensive applications, e.g., telecommunication and high-throughput drug screening. Magnetic suspension array technology may offer intrinsic advantages to screening applications by enabling high distinguishability, the ease of code generation, and the feasibility of fast code readout, though the practical applicability of magnetic suspension array technology remains hampered by the lack of quality administration of encoded microcarriers. Here, a logic-controlled microfluidic system enabling controlled synthesis of magnetic suspension arrays in multiphase flow networks is realized. The smart and compact system offers a practical solution for the quality administration and screening of encoded magnetic microcarriers and addresses the universal need of process control for synthesis in microfluidic networks, i.e., on-demand creation of droplet templates for high information capacity. The demonstration of magnetic suspension array technology enabled by magnetic in-flow cytometry opens the avenue toward point-of-care multiplexed bead-based assays, clinical diagnostics, and drug discovery.

Stretchable electronics1, 2 is one of the most vital technological research fields of the latest years, aiming to revolutionize custom electronic systems toward being arbitrarily reshapeable on demand after their fabrication. This opens up novel application potentials for multifunctional high‐speed electronic systems like smart skins,3, 4 active medical implants,5, 6 soft robotics,7, 8 or stretchable consumer electronics.9, 10 A variety of functional components that can be subjected to high tensile deformations have already been introduced, including light emitting diodes,11 solar cells,10 pressure and temperature sensors,12 integrated circuitry,13 batteries,14, 15 antennas,16 and many more. Introducing stretchable highly sensitive magnetosensorics into the family of stretchable electronics17 was envisioned to equip this novel electronic platform with magnetic functionalities. This can be of particular interest for smart skin and biomedical applications promoted by very recent developments of imperceptible12 and transient6 electronics, as magnetoelectronic components can add a sense of orientation, displacement, and touchless interaction.

We report a magnetofluidic device with integrated strong ferromagnetically-coupled and hysteresis-free spin valve sensors for dynamic monitoring of ferrofluid droplets in microfluidics. The strong ferromagnetic coupling between the free layer and the pinned layer of spin valve sensors is achieved by reducing the spacer thickness, while the hysteresis of the free layer is eliminated by the interplay between shape anisotropy and the strength of coupling. The increased ferromagnetic coupling field up to the remarkable 70 Oe, which is five-times larger than conventional solutions, brings key advantages for dynamic sensing, e.g., a larger biasing field giving rise to larger detection signals, facilitating the operation of devices without saturation of the sensors. Studies on the fundamental effects of an external magnetic field on the evolution of the shape of droplets, as enabled by the non-visual monitoring capability of the device, provides crucial information for future development of a magnetofluidic device for multiplexed assays.

The flourishing and eagerness of portable consumer electronics necessitates functional elements to be lightweight, flexible, and even wearable (Figure 1) [1], fulfilling the needs of soft robotics, medical implants, imperceptible and transient electronics [2-4]. Next generation flexible appliances aim to become fully autonomous and will require ultra-thin and flexible navigation modules, body tracking and relative position monitoring systems. Key building blocks of navigation and position tracking devices are the magnetic field sensors.

A flexible diagnostic platform is realized and its performance is demonstrated for early detection of avian influenza virus (AIV) subtype H1N1 DNA sequences. The key component of the platform is high-performance biosensors based on high output currents and low power dissipation Si nanowire field effect transistors (SiNW-FETs) fabricated on flexible 100 μm thick polyimide foils. The devices on a polymeric support are about ten times lighter compared to their rigid counterparts on Si wafers and can be prepared on large areas. While the latter potentially allows reducing the fabrication costs per device, the former makes them cost efficient for high-volume delivery to medical institutions in, e.g., developing countries. The flexible devices withstand bending down to a 7.5 mm radius and do not degrade in performance even after 1000 consecutive bending cycles. In addition to these remarkable mechanical properties, on the analytic side, the diagnostic platform allows fast detection of specific DNA sequences of AIV subtype H1N1 with a limit of detection of 40 × 10(-12) m within 30 min suggesting its suitability for early stage disease diagnosis.

Topological magnetic states, such as chiral skyrmions, are of great scientific interest and show huge potential for novel spintronics applications, provided their topological charges can be fully controlled. So far skyrmionic textures have been observed in noncentrosymmetric crystalline materials with low symmetry and at low temperatures. We propose theoretically and demonstrate experimentally the design of spin textures with topological charge densities that can be tailored at ambient temperatures. Tuning the interlayer coupling in vertically stacked nanopatterned magnetic heterostructures, such as a model system of a Co/Pd multilayer coupled to Permalloy, the in-plane non-collinear spin texture of one layer can be imprinted into the out-of-plane magnetised material. We observe distinct spin textures, e.g. vortices, magnetic swirls with tunable opening angle, donut states and skyrmion core configurations. We show that applying a small magnetic field, a reliable switching between topologically distinct textures can be achieved at remanence.

We present a concept of multidimensional magnetic and optical barcoding of droplets based on a magnetofluidic platform. The platform comprises multiple functional areas, such as an encoding area, an encoded droplet pool and a magnetic decoding area with integrated giant magnetoresistive (GMR) sensors. To prove this concept, penicillin functionalized with fluorescent dyes is coencapsulated with magnetic nanoparticles into droplets. While fluorescent dyes are used as conventional optical barcodes which are decoded with an optical decoding setup, an additional dimensionality of barcodes is created by using magnetic nanoparticles as magnetic barcodes for individual droplets and integrated micro-patterned GMR sensors as the corresponding magnetic decoding devices. The strategy of incorporating a magnetic encoding scheme provides a dynamic range of ~40 dB in addition to that of the optical method. When combined with magnetic barcodes, the encoding capacity can be increased by more than 1 order of magnitude compared with using only optical barcodes, that is, the magnetic platform provides more than 10 unique magnetic codes in addition to each optical barcode. Besides being a unique magnetic functional element for droplet microfluidics, the platform is capable of on-demand facile magnetic encoding and real-time decoding of droplets which paves the way for the development of novel non-optical encoding schemes for highly multiplexed droplet-based biological assays.

A grand vision of realization of smart and compact multifunctional microfluidic devices for wearable health monitoring, environment sensing and point-of-care tests emerged with the fast development of flexible electronics. As a vital component towards this vision, magnetic functionality in flexible fluidics is still missing although demanded by the broad utility of magnetic nanoparticles in medicine and biology. Here, we demonstrate the first flexible microfluidic analytic device with integrated high-performance giant magnetoresistive (GMR) sensors. This device can be bent to a radius of 2 mm while still retaining its full performance. Various dimensions of magnetic emulsion droplets can be probed with high precision using a limit of detection of 0.5 pl, providing broad applicability in high-throughput droplet screening, flow cytometry and drug development. The flexible feature of this analytic device holds great promise in the realization of wearable, implantable multifunctional platforms for biomedical, pharmaceutical and chemical applications.

We realize a magnetoresistive emulsion analyzer capable of detection, multiparametric analysis and sorting of ferrofluid-containing nanoliter-droplets. The operation of the device in a cytometric mode provides high throughput and quantitative information about the dimensions and magnetic content of the emulsion. Our method offers important complementarity to conventional optical approaches involving ferrofluids, and paves the way to the development of novel compact tools for diagnostics and nanomedicine including drug design and screening.