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Regulation of genetic activity in single cells and tissues is pivotal to determine key cellular functions in current biomedicine, yet the conventional biochemical activators lack spatiotemporal precision due to the diffusion-mediated slow kinetics and nonselectivity. Here, we describe a magnetogenetic method for target-specific activation of a clustered regularly interspaced short palindromic repeats (CRISPR) system for the regulation of intracellular proteins. We used magnetomechanical force generated by the magnetic nanostructure to activate pre-encoded Piezo1, the mechanosensitive ion channel, on the target cell. The activated Piezo1 further triggers the intracellular Ca

Lipid rafts are small and dynamic membrane compartments that are enriched with cholesterols or sphingolipids. The coalescence of small lipid rafts into a large lipid raft forms a signaling platform at the immunological synapse that plays a crucial role in controlling T cell activation. Cholesterol is a major component for the formation and function of lipid rafts, but the relationship between the spatial configuration of cholesterols and the lipid raft mediated membrane segregation as well as TCR signaling remains poorly understood. Here we used cholesterol conjugated DNA origami nanostructures, cholesterol nano-patch (CNP) to construct lipid rafts on intact live T cells. CNPs are two-dimensional DNA scaffolds that allow controlling the spatial presentation of cholesterols in the plasma membrane. CNPs efficiently bind onto the T cell membrane and rapidly induce large, polarized membrane cap structures which colocalize with flotillin-1. These CNP mediated membrane segregations, which we define as synthetic lipid rafts, drive membrane segregation of key signaling molecules including TCR and CD45, thereby triggering downstream TCR signaling and subsequently functional T cell responses without antigenic challenges. Our work highlights the potential of CNP in uncovering the mechanisms that lipid rafts induced by cholesterols drive membrane protein reorganization and control T cell signaling, and offers valuable insights into the design of antigen-independent immunotherapies.

We investigated the magnetic effect of Mn2+ ions on an exciton of Mn-doped CsPbI3 quantum dots (QDs), where we looked for the signatures of an exciton magnetic polaron known to produce a large effective magnetic field in Mn-doped CdSe QDs. In contrast to Mn-doped CdSe QDs that can produce ∼100 T of magnetic field upon photoexcitation, manifested as a large change in the energy and relaxation dynamics of a bright exciton, Mn-doped CsPbI3 QDs exhibited little influence of a magnetic dopant on the behavior of a bright exciton. However, a μs-lived dark exciton in CsPbI3 QDs showed 40% faster decay in the presence of Mn2+, equivalent to the effect of ∼3 T of an external magnetic field. While further study is necessary to fully understand the origin of the large difference in the magneto-optic property of an exciton in two systems, we consider that the difference in antiferromagnetic coupling of the dopants is an important contributing factor.

ConspectusThe modern healthcare system faces an unrelenting threat from microorganisms, as evidenced by global outbreaks of new viral diseases, emerging antimicrobial resistance, and the rising incidence of healthcare-associated infections (HAIs). An effective response to these threats requires rapid and accurate diagnostic tests that can identify causative pathogens at the point of care (POC). Such tests could eliminate diagnostic uncertainties, facilitating patient triaging, minimizing the empiric use of antimicrobial drugs, and enabling targeted treatments. Current standard methods, however, often fail to meet the needs of rapid diagnosis in POC settings. Culture-based assays entail long processing times and require specialized laboratory infrastructure; nucleic acid (NA) tests are often limited to centralized hospitals due to assay complexity and high costs. Here we discuss two new POC tests developed in our groups to enable the rapid diagnosis of infection. The first is nanoPCR that takes advantages of core-shell magnetoplasmonic nanoparticles (MPNs): (i) Au shell significantly accelerates thermocycling via volumetric, plasmonic light-to-heat conversion and (ii) a magnetic core enables sensitive in situ fluorescent detection via magnetic clearing. By adopting a Ferris wheel module, the system expedites multisamples in parallel with a minimal setup. When applied to COVID-19 diagnosis, nanoPCR detected SARS-CoV-2 RNA down to 3.2 copy/μL within 17 min. In particular, nanoPCR diagnostics accurately identified COVID-19 cases in clinical samples (n = 150), validating its clinical applicability. The second is a polarization anisotropy diagnostic (PAD) system that exploits the principle of fluorescence polarization (FP) as a detection modality. Fluorescent probes were designed to alter their molecular weight upon recognizing target NAs. This event modulates the probes' tumbling rate (Brownian motion), which leads to changes in FP. The approach is robust against environmental noise and benefits from the ratiometric nature of the signal readout. We applied PAD to detect clinically relevant HAI bacteria (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus). The PAD assay demonstrated detection sensitivity down to the single bacterium level and determined both drug resistance and virulence status. In summary, these new tests have the potential to become powerful tools for rapid diagnosis in the infectious disease space. They do not require highly skilled personnel or labor-intensive analyses, and the assays are quick and cost-effective. These attributes will make nanoPCR and PAD well-aligned with a POC workflow to aid physicians to initiate prompt and informed patient treatment.

Nanoparticles with multifunctionality and high colloidal stability are essential for biomedical applications. However, their use is often hindered by the formation of thick coating shells and/or nanoparticle agglomeration. Herein, we report a single nanoparticle coating strategy to form 1 nm polymeric shells with a variety of chemical functional groups and surface charges. Under exposure to alternating magnetic field, nanosecond thermal energy pulses trigger a polymerization in the region only a few nanometers from the magnetic nanoparticle (MNP) surface. Modular coatings containing functional groups, according to the respective choice of monomers, are possible. In addition, the surface charge can be tuned from negative through neutral to positive. We adopted a coating method for use in biomedical targeting studies where obtaining compact nanoparticles with the desired surface charge is critical. A single MNP with a zwitterionic charge can provide excellent colloidal stability and cell-specific targeting.

Contrast agents for magnetic resonance imaging (MRI) improve anatomical visualizations. However, owing to poor image resolution in whole-body MRI, resolving fine structures is challenging. Here, we report that a nanoparticle with a polysaccharide supramolecular core and a shell of amorphous-like hydrous ferric oxide generating strong T1 MRI contrast (with a relaxivity coefficient ratio of ~1.2) facilitates the imaging, at resolutions of the order of a few hundred micrometres, of cerebral, coronary and peripheral microvessels in rodents and of lower-extremity vessels in rabbits. The nanoparticle can be synthesized at room temperature in aqueous solution and in the absence of surfactants, has blood circulation and renal clearance profiles that prevent opsonization, and leads to better imaging performance than Dotarem (gadoterate meglumine), a clinically approved gadolinium-based MRI contrast agent. The nanoparticle's biocompatibility and imaging performance may prove advantageous in a broad range of preclinical and clinical applications of MRI.

Among physical stimulation modalities, magnetism has clear advantages, such as deep penetration and untethered interventions in biological subjects. However, some of the working principles and effectiveness of existing magnetic neurostimulation approaches have been challenged, leaving questions to be answered. Here we introduce m-Torquer, a magnetic toolkit that mimics magnetoreception in nature. It comprises a nanoscale magnetic torque actuator and a circular magnet array, which deliver piconewton-scale forces to cells over a working range of ~70 cm. With m-Torquer, stimulation of neurons expressing bona fide mechanosensitive ion channel Piezo1 enables consistent and reproducible neuromodulation in freely moving mice. With its long working distance and cellular targeting capability, m-Torquer provides versatility in its use, which can range from single cells to in vivo systems, with the potential application in large animals such as primates. A magnetic torque actuator has been developed and is capable of modulation of neurons expressing the mechanosensitive ion channel, Piezo1, resulting in long-distance control of locomotion of mice.

Well-defined recyclable Pd- and Rh-bipyridyl group-impregnated SBA-15 catalysts were prepared for C-C bond coupling reaction and selective hydrogenation reactions, respectively. These SBA-15 derived ligands for the catalysts were prepared by direct and indirect co-condensation method using bipyridyl-linked methallylsilane. This indirect method, involving methoxysilane generated from methallylsilane shows higher loading efficiency of transition metal catalysts on SBA-15 than the direct use of methallylsilane.

The current gold standard for COVID-19 confirmation is RT-PCR, which possesses high sensitivity and specificity, but a long turnaround time has been a drawback. Here, we introduce a nanoPCR platform that can yield breakthroughs in RT-PCR speed and decentralize the diagnostic testing. A key innovation is to exploit magneto-plasmonic nanoparticles for dual purposes: fast thermocycling through plasmonic heating and enhanced signal detection via magnetic fluorescence switch. We further integrated these functionalities into a portable system to streamline point-of-care (POC) COVID-19 diagnostics with a “one-step-finish” approach from sampling to result. When applied with clinical COVID-19 samples, nanoPCR achieved an analytical performance of sensitivity and specificity comparable to that of a benchtop instrument but completed the entire detection within 18 minutes (vs. 2.5 hours for regular RT-PCR), which makes it ideal for rapid POC diagnostics. This platform technology is readily scalable for higher throughput and expandable to other disease targets, promising broader impacts in on-site molecular testing.

There has been a great deal of interest in designing soft robots that can mimic a human system with haptic and proprioceptive functions. There is now a strong demand for soft robots that can sense their surroundings and functions in harsh environments. This is because the wireless sensing and actuating capabilities of these soft robots are very important for monitoring explosive gases in disaster areas and for moving through contaminated environments. To develop these wireless systems, complex electronic circuits must be integrated with various sensors and actuators. However, the conventional electronic circuits based on silicon are rigid and fragile, which can limit their reliable integration with soft robots for achieving continuous locomotion. In our study, we developed an untethered, soft robotic hand that mimics human fingers. The soft robotic fingers are composed of a thermally responsive elastomer composite that includes capsules of ethanol and liquid metals for its shape deformation through an electrothermal phase transition. And these soft actuators are integrated fully with flexible forms of heaters, with pressure, temperature, and hydrogen gas sensors, and wireless electronic circuits. Entire functions of this soft hand, including the gripping motion of soft robotic fingers and the real-time detections of tactile pressures, temperatures, and hydrogen gas concentrations, are monitored or controlled wirelessly using a smartphone. This wireless sensing and actuating system for somatosensory and respiratory functions of a soft robot provides a promising strategy for next-generation robotics.

Nanoscale dynamic processes such as the diffusion of ions within solid-state structures are critical for understanding and tuning material properties in a wide range of areas, such as energy storage and conversion, catalysis, and optoelectronics. In the generation of new types of nanocrystals (NCs), diffusion-mediated ion exchange reactions have also been proposed as one of the most effective transformational strategies. However, retaining the original morphology and crystal structure of metal oxide NCs has been challenging because of Kirkendall void formation, and there has been no success, especially for anion exchange. Here we show that with the aid of an oxygen extracting reagent (OER), anion diffusion is dramatically accelerated and morphology-conserving anion exchange without Kirkendall void formation is possible. In the case of the conversion of Fe

We investigated the magnetic effect of Mn

Adherens junctions (AJs) create spatially and mechanically discrete microdomains at the interfaces of cells. Using a mechanogenetic platform that generates artificial AJs with controlled protein localization, clustering, and mechanical loading, we report that AJs also organize proteolytic hotspots for γ-secretase with a spatially-regulated substrate selectivity that is critical in the processing of Notch and other transmembrane proteins. Membrane microdomains outside of AJs exclusively organize Notch ligand-receptor engagement (LRE-µdomain) to initialize receptor activation. Conversely, membrane microdomains within AJs exclusively serve to coordinate regulated intramembrane proteolysis (RIP-µdomain). They do so by concentrating γ-secretase and primed receptors while excluding full-length Notch. AJs induce these functionally distinct microdomains by means of cholesterol-dependent γ-secretase recruitment and size-dependent protein segregation. By excluding full-length Notch from RIP-µdomains, AJs prevents inappropriate enzyme-substrate interactions and suppresses spurious Notch activation. Ligand-induced ectodomain shedding eliminates size-dependent segregation, releasing Notch to translocate into AJs for processing by γ-secretase. This mechanism directs radial differentiative expansion of ventricular zone-neural progenitor cells in vivo and more broadly regulates the proteolysis of large cell-surface receptors like amyloid precursor protein. These findings suggest an unprecedented role of AJs in creating size-selective spatial switches that choreograph γ-secretase processing of multiple transmembrane proteins regulating development, homeostasis, and disease.

Tetrahydrocannabinol (THC), the primary psychoactive ingredient of cannabis, impairs cognitive and motor function in a concentration-dependent fashion. Drug testing is commonly performed for employment and law enforcement purposes; however, available tests produce low-sensitive binary results (lateral flow assays) or have long turnaround (gas chromatography-mass spectrometry). To enable on-site THC quantification in minutes, we developed a rapid assay for oral THC analysis called EPOCH, express probe for on-site cannabis inhalation. EPOCH features distinctive sensor design such as a radial membrane and transmission optics, all contained in a compact cartridge. This integrated approach permitted assay completion within 5 minutes with a detection limit of 0.17 ng/mL THC, which is below the regulatory guideline (1 ng/mL). As a proof of concept for field testing, we applied EPOCH to assess oral fluid samples from cannabis users (n = 43) and controls (n = 43). EPOCH detected oral THC in all specimens from cannabis smokers (median concentration, 478 ng/mL) and THC-infused food consumers. Longitudinal monitoring showed a fast drop in THC concentrations within the first 6 hours of cannabis smoking (half-life, 1.4 hours).

Adherens junctions (AJs) create spatially, chemically and mechanically discrete microdomains at cellular interfaces. Here, using a mechanogenetic platform that generates artificial AJs with controlled protein localization, clustering and mechanical loading, we find that AJs also organize proteolytic hotspots for γ-secretase with a spatially regulated substrate selectivity that is critical in the processing of Notch and other transmembrane proteins. Membrane microdomains outside of AJs exclusively organize Notch ligand-receptor engagement (LRE microdomains) to initiate receptor activation. Conversely, membrane microdomains within AJs exclusively serve to coordinate regulated intramembrane proteolysis (RIP microdomains). They do so by concentrating γ-secretase and primed receptors while excluding full-length Notch. AJs induce these functionally distinct microdomains by means of lipid-dependent γ-secretase recruitment and size-dependent protein segregation. By excluding full-length Notch from RIP microdomains, AJs prevent inappropriate enzyme-substrate interactions and suppress spurious Notch activation. Ligand-induced ectodomain shedding eliminates size-dependent segregation, releasing Notch to translocate into AJs for processing by γ-secretase. This mechanism directs radial differentiation of ventricular zone-neural progenitor cells in vivo and more broadly regulates the proteolysis of other large cell-surface receptors such as amyloid precursor protein. These findings suggest an unprecedented role of AJs in creating size-selective spatial switches that choreograph γ-secretase processing of multiple transmembrane proteins regulating development, homeostasis and disease.

Tactile pressure sensors as flexible bioelectronic devices have been regarded as the key component for recently emerging applications in electronic skins, health-monitoring devices, or human-machine interfaces. However, their narrow range of sensible pressure and their difficulty in forming high integrations represent major limitations for various potential applications. Herein, we report fully integrated, active-matrix arrays of pressure-sensitive MoS2 transistors with mechanoluminescent layers and air dielectrics for wide detectable range from footsteps to cellular motions. The inclusion of mechanoluminescent materials as well as air spaces can increase the sensitivity significantly over entire pressure regimes. In addition, the high integration capability of these active-matrix sensory circuitries can enhance their spatial resolution to the level sufficient to analyze the pressure distribution in a single cardiomyocyte. We envision that these wide-range pressure sensors will provide a new strategy toward next-generation electronics at biomachine interfaces to monitor various mechanical and biological phenomena at single-cell resolution.

While neural cell transplantation represents a promising therapy for neurodegenerative diseases, the formation of functional networks of transplanted cells with host neurons constitutes one of the challenging steps. Here, we introduce a magnetic guidance methodology that controls neurite growth signaling via magnetic nanoparticles (MNPs) conjugated with antibodies targeting the deleted in colorectal cancer (DCC) receptor (DCC-MNPs). Activation of the DCC receptors by clusterization and subsequent axonal growth of the induced neuronal (iN) cells was performed in a spatially controlled manner. In addition to the directionality of the magnetically controlled axon projection, axonal growth of the iN cells assisted the formation of functional connections with pre-existing primary neurons. Our results suggest magnetic guidance as a strategy for improving neuronal connectivity by spatially guiding the axonal projections of transplanted neural cells for synaptic interactions with the host tissue.

Wireless communication through linkage with a smartphone and other portable devices in the sensor area are essential for increasing the efficiency of utilization by storing sensing-value data. Thus, the demand for wireless technology is increasing due to the advantages it provides for the various applications that use these data. However, there is still considerable ambiguity concerning the low portability of such technology due to the increased volume with component integration, the high consumption of power, and the necessity of having a separate battery. Herein, we present solutions for these problems with demonstrations that involve 1) the miniaturization of the device by altering the structure of the built-in battery, 2) the use of a pressure-activated switch for the low-power driving technology, and 3) the implementation of a wireless communication platform by integrating a Bluetooth module with the devices. In addition, we demonstrate a human-interactive display that enables users to instantly observe the changes in the brightness of the organic light-emitting diodes (OLED) as the pressure changes. We show that the system can display the measured, real-time pressure values on the screens of mobile devices, which represents a significant advancement in the fields of energy science and biomedical science.

Multifunctional magnetic nanoparticles have shown great promise as next-generation imaging and perturbation probes for deciphering molecular and cellular processes. As a consequence of multicomponent integration into a single nanosystem, pre-existing nanoprobes are typically large and show limited access to biological targets present in a crowded microenvironment. Here, we apply organic-phase surface PEGylation, click chemistry, and charge-based valency discrimination principles to develop compact, modular, and monovalent magnetofluorescent nanoparticles (MFNs). We show that MFNs exhibit highly efficient labeling to target receptors present in cells with a dense and thick glycocalyx layer. We use these MFNs to interrogate the E-cadherin-mediated adherens junction formation and F-actin polymerization in a three-dimensional space, demonstrating the utility as modular and versatile mechanogenetic probes in the most demanding single-cell perturbation applications.

Scanning probe microscopy techniques, such as atomic force microscopy and scanning tunnelling microscopy, are harnessed to image nanoscale structures with an exquisite resolution, which has been of significant value in a variety of areas of nanotechnology. These scanning probe techniques, however, are not generally suitable for high-throughput imaging, which has, from the outset, been a primary challenge. Traditional approaches to increasing the scalability have involved developing multiple probes for imaging, but complex probe design and electronics are required to carry out the detection method. Here, we report a probe-based imaging method that utilizes scalable cantilever-free elastomeric probe design and hierarchical measurement architecture, which readily reconstructs high-resolution and high-throughput topography images. In a single scan, we demonstrate imaging with a 100-tip array to obtain 100 images over a 1-mm2 area with 106 pixels in less than 10 min. The potential for large-scale tip integration and the advantage of a simple probe array suggest substantial promise for our approach to high-throughput imaging far beyond what is currently possible.

ConspectusInorganic nanocrystal design has been continuously evolving with a better understanding of the chemical reaction mechanisms between chemical stimuli and nanocrystals. Under certain conditions, molecular compounds can be effective as chemical stimuli to induce transformative reactions of nanocrystals toward new materials that would differ in geometric shape, composition, and crystallographic structure. To explore such evolutionary processes, two-dimensional (2D) layered transition-metal chalcogenide (TMC) nanostructures are an interesting structural platform because they not only exhibit unique transformation pathways due to their structural anisotropy but also present new opportunities for improved material properties for potential applications such as catalysis and energy conversion and storage. The high surface area/volume ratio, interlayer van der Waals (vdW) spacing, and different coordination states between the unsaturated edges and the fully saturated basal planes of the chalcogens are characteristic of 2D layered TMC nanostructures, which subsequently lead to anisotropic chemical processes during chemical transformations, such as regioselective reactions at the interfacial boundaries in the pathways for either porous or solid heteronanostructures. In this Account, we first discuss the chemical reactivity of 2D layered TMC nanostructures. By categorizing the external stimuli in terms of chemical principles, such as Lewis acid-base chemistry, a desirable regioselective chemical reaction can occur with controlled reactivity. In association with the knowledge obtained from the nanoscale chemical reactivity of 2D layered nanocrystals, similar efforts in other important morphologies such as 1D and isotropic 0D nanocrystals are introduced. For instance, for 1D and 0D metal oxide nanocrystals, the effects of molecular stimuli on the atomic-level changes in the crystal lattice are demonstrated, eventually leading to a variety of shape transformations.

Ideal electromagnetic (EM) wave absorbers can absorb all incident EM waves, regardless of the incident direction, polarization, and frequency. Absorptance and reflectance are intrinsic material properties strongly correlated with electrical conductivity; hence, achieving perfect absorptance with zero reflectance is challenging. Herein, we present a design strategy for preparing a nearly ideal EM absorber based on a layered metal that maximizes absorption by utilizing multiple internal reflections and minimizes reflection using a monotonic gradient of intrinsic impedance. This approach was experimentally verified using aluminum nanoflakes prepared via topochemical etching of lithium from Li9Al4, and the impedance-graded structure was obtained through the size-based sorting behavior of aluminum nanoflakes sinking in dispersion. Unlike in traditional shielding materials, strong absorption (26.76 dB) and negligible reflectivity (0.04 dB) with a ratio of >103 can be achieved in a 120 μm thick film. Overall, our findings exhibit potential for developing a novel class of antireflective shielding materials.

The fine structure of the band edge exciton and the dark exciton photoluminescence (PL) are topics of significant interest in the research of semiconducting metal halide perovskite nanocrystals, with several conflicting reports on the level ordering of the bright and dark states and the accessibility of the emitting dark states. Recently, we observed the intense dark exciton PL in strongly confined CsPbBr3 nanocrystals at cryogenic temperatures, in contrast to weakly confined nanocrystals lacking dark exciton PL, which was explained by the confinement enhanced bright-dark exciton splitting. In this work, we investigated the size-dependence of the dark exciton photoluminescence properties in CsPbBr3 and CsPbI3 quantum dots in the strongly confined regime, showing the clear role of confinement in determining the bright-dark energy splitting (ΔEBD) and the dark exciton lifetime (τD). We observe the increase in both ΔEBD and τD with increasing quantum confinement in CsPbBr3 and CsPbI3 QDs, consistent with the earlier predictions on the size-dependence of ΔEBD and τD. Our results show that quantum confinement plays a crucial role in determining the accessibility to the dark exciton PL and its characteristics in metal halide perovskite nanocrystals.

This study presents a smart, soft contact lens that provides real-time sensing for the wireless immunosensing of cortisol., Despite various approaches to immunoassay and chromatography for monitoring cortisol concentrations, conventional methods require bulky external equipment, which limits their use as mobile health care systems. Here, we describe a human pilot trial of a soft, smart contact lens for real-time detection of the cortisol concentration in tears using a smartphone. A cortisol sensor formed using a graphene field-effect transistor can measure cortisol concentration with a detection limit of 10 pg/ml, which is low enough to detect the cortisol concentration in human tears. In addition, this soft contact lens only requires the integration of this cortisol sensor with transparent antennas and wireless communication circuits to make a smartphone the only device needed to operate the lens remotely without obstructing the wearer’s view. Furthermore, in vivo tests using live rabbits and the human pilot experiment confirmed the good biocompatibility and reliability of this lens as a noninvasive, mobile health care solution.

Aberrant cleavage of Notch by γ-secretase is implicated in numerous diseases, but how cleavage is regulated in space and time is unclear. Here, we report that cadherin-based adherens junctions (cadAJs) are sites of high cell-surface γ-secretase activity, as well as sites of constrained physical space that excludes γ-secretase substrates having large extracellular domains (ECDs) like Notch. ECD shedding initiates drastic spatial relocalization of Notch to cadAJs, allowing enzyme-substrate interactions and downstream signaling. Spatial mutations by adjusting the ECD size or the physical constraint alter signaling. Dysregulation of this spatial switch promotes precocious differentiation of ventricular zone neural progenitor cells in vivo. We show the generality of this spatial switch for amyloid precursor protein proteolysis. Thus, cadAJs create spatially distinct biochemical compartments regulating cleavage events involving γ-secretase and preventing aberrant activation of receptors.

The ability to sense and manipulate the state of biological systems has been extensively advanced during the last decade with the help of recent developments in physical tools. Unlike standard genetic and pharmacological perturbation techniques – knockdown, overexpression, small molecule inhibition – that provide a basic on/off switching capability, these physical tools provide the capacity to control the spatial, temporal, and mechanical properties of the biological targets. Among the various physical cues, magnetism offers distinct advantages over light or electricity. Magnetic fields freely penetrate biological tissues and are already used for clinical applications. As one of the unique features, magnetic fields can be transformed into mechanical stimuli which can serve as a cue in regulating biological processes. However, their biological applications have been limited due to a lack of high-performance magnetism-to-mechanical force transducers with advanced spatiotemporal capabilities. In this account, we present recent developments in magnetic nano-tweezers (MNTs) as a high-performance tool for interrogating the spatiotemporal control of cells in living tissue. MNTs are comprised of force-generating magnetic nanoparticles and field generators. Through proper design and the integration of individual components, MNTs deliver controlled mechanical stimulation to targeted biomolecules at any desired space and time. We first discuss about MNT configuration with different force-stimulation modes. By modulating geometry of the magnetic field generator, MNTs exert pulling, dipole-dipole attraction, and rotational forces to the target specifically and quantitatively. We discuss the key physical parameters determining force magnitude, which include magnetic field strength, magnetic field gradient, magnetic moment of the magnetic particle, as well as distance between the field generator and the particle. MNTs also can be used over a wide range of biological time scales — By simply adjusting the amplitude and phase of the applied current, MNTs based on electromagnets allow for dynamic control of the magnetic field from microseconds to hours. Chemical design and the nanoscale effects of magnetic particles are also essential for optimizing MNT performance. We discuss key strategies to develop magnetic nanoparticles with improved force-generation capabilities with a particular focus on the effects of size, shape, and composition of the nanoparticles. We then introduce various strategies and design considerations for target-specific biomechanical stimulations with MNTs. One-to-one particle-receptor engagement for delivering a defined force to the targeted receptor and the small size of the nanoparticles are important. Finally, we demonstrate the utility of MNTs for manipulating biological functions and activities with various spatial (single molecule/cell to organisms) and temporal resolution (microseconds to days). MNTs have the potential to be utilized in many exciting applications across diverse biological systems spanning from fundamental biology investigations of spatial and mechanical signaling dynamics at the single-cell and systems levels to in vivo therapeutic applications.

Pathogen activated antibody-secreting cells (ASCs) produce and secrete antigen-specific antibodies. ASCs are detectable in the peripheral blood as early as 3 days after antigen exposure, which makes ASCs a potential biomarker for early disease detection. Here we present a Magnetic Capture and Detection (MCD) assay for sensitive, on-site detection of ASCs. In this approach, ASCs are enriched through magnetic capture, and secreted antibodies are magnetically detected by a miniaturized nuclear magnetic resonance (μNMR) system. This approach is based entirely on magnetics which supports high contrast against biological background, and simplifies assay procedures. We advanced the MCD system by i) synthesizing magnetic nanoparticles (MNPs) with high magnetic moments for both cell capture and antibody detection, ii) developing a miniaturized magnetic device for high-yield cell capture, and iii) optimizing the μNMR assay for antibody detection. Antibody responses targeting hemolysin E (HlyE) can accurately identify individuals with acute enteric fever. As a proof-of-concept, we applied MCD to detect antibodies produced by HlyE-specific hybridoma cells. The MCD achieved high sensitivity in detecting antibodies secreted from as few as 5 hybridoma cells (50 cells/mL). Importantly, the assay could be performed with whole blood with minimal sample processing.

Because of the absence of native dangling bonds on the surface of the layered transition metal dichalcogenides (TMDCs), the surface of colloidal quantum dots (QDs) of TMDCs is exposed directly to the solvent environment. Therefore, the optical and electronic properties of TMDCS QDs are expected to have stronger influence from the solvent than usual surface-passivated QDs due to more direct solvent-QD interaction. Study of such solvent effect has been difficult in colloidal QDs of TMDC due to the large spectroscopic heterogeneity resulting from the heterogeneity of the lateral size or (and) thickness in ensemble. Here, we developed a new synthesis procedure producing the highly uniform colloidal monolayer WS2 QDs exhibiting well-defined photoluminescence (PL) spectrum free from ensemble heterogeneity. Using these newly synthesized monolayer WS2 QDs, we observed the strong influence of the aromatic solvents on the PL energy and intensity of monolayer WS2 QD beyond the simple dielectric screening effect, whi...

Magnetic nanoparticle (MNP)-mediated heating systems have emerged as an effective strategy for the fine control of biological systems from hyperthermia to cell signaling in a spatiotemporally controlled fashion. To achieve satisfactory performance, advanced design concepts have been developed to tailor the magnetism that directly affects the heating properties of nanoparticles. In this review, we focus on recent advances in magnetism-engineered nanoparticles. Fundamental principles of magnetic heating mechanisms and related key magnetic parameters are discussed first to provide instructive guidelines for the design of MNPs with enhanced heating efficiency. Then, we highlight recent progress in MNPs for optimized heat generation with unique design approaches to control magnetism. Finally, we discuss highly effective biomedical application studies such as dual-mode magnetic hyperthermia, magnetothermally triggered drug delivery, and the magnetothermal control of cellular activities.

Developing innovative tools that facilitate the understanding of sophisticated biological systems has been one of the Holy Grails in the physical and biological sciences. In this Commentary, we discuss recent advances, opportunities, and challenges in the use of nanomaterials as a precision tool for biology and medicine.

Dark ground state exciton in semiconductor nanocrystals has been a subject of much interest due to its long lifetime attractive for applications requiring long-lived electronic or spin states. Significant effort has been made recently to explore and access the dark exciton level in metal halide perovskite nanocrystals, which are emerging as a superior source of photons and charges compared to other existing semiconductor nanocrystals. However, the direct observation of long-lived photoluminescence from dark exciton has remained elusive in metal halide perovskite nanocrystals. Here, we report the observation of the intense emission from dark ground state exciton with 1-10 us lifetime in strongly quantum confined CsPbBr3 nanocrystals, which contrasts the behavior of weakly confined system explored so far. The study in CsPbBr3 nanocrystals with varying degree of confinement has revealed the crucial role of quantum confinement in enhancing the bright-dark exciton level splitting which is important for accessing the dark exciton. Our work demonstrates the future potential of strongly quantum-confined perovskite nanocrystals as a new platform to utilize dark excitons.

Recent suggestions of nanoscale heat confinement on the surface of synthetic and biogenic magnetic nanoparticles during heating by radio frequency-alternating magnetic fields have generated intense interest because of the potential utility of this phenomenon for noninvasive control of biomolecular and cellular function. However, such confinement would represent a significant departure from the classical heat transfer theory. Here, we report an experimental investigation of nanoscale heat confinement on the surface of several types of iron oxide nanoparticles commonly used in biological research, using an all-optical method devoid of the potential artifacts present in previous studies. By simultaneously measuring the fluorescence of distinct thermochromic dyes attached to the particle surface or dissolved in the surrounding fluid during radio frequency magnetic stimulation, we found no measurable difference between the nanoparticle surface temperature and that of the surrounding fluid for three distinct nanoparticle types. Furthermore, the metalloprotein ferritin produced no temperature increase on the protein surface nor in the surrounding fluid. Experiments mimicking the designs of previous studies revealed potential sources of the artifacts. These findings inform the use of magnetic nanoparticle hyperthermia in engineered cellular and molecular systems.

Contrast agents for magnetic resonance imaging (MRI) improve anatomical visualizations. However, owing to poor image resolution in whole-body MRI, resolving fine structures is challenging. Here, we report that a nanoparticle with a polysaccharide supramolecular core and a shell of amorphous-like hydrous ferric oxide generating strong T

Tactile pressure sensors as flexible bioelectronic devices have been regarded as the key component for recently emerging applications in electronic skins, health-monitoring devices, or human-machine interfaces. However, their narrow range of sensible pressure and their difficulty in forming high integrations represent major limitations for various potential applications. Herein, we report fully integrated, active-matrix arrays of pressure-sensitive MoS

A flexible magnetic wire inserted in a blood vessel improves the capture of magnetically labelled circulating tumour cells.

Multidrug resistance (MDR) is a leading cause of failure in current chemotherapy treatment and constitutes a formidable challenge in therapeutics. Here, we demonstrate that a nanoscale magnetic tandem apoptosis trigger (m-TAT), which consists of a magnetic nanoparticle and chemodrug (e.g., doxorubicin), can completely remove MDR cancer cells in both in vitro and in vivo systems. m-TAT simultaneously activates extrinsic and intrinsic apoptosis signals in a synergistic fashion and downregulates the drug efflux pump (e.g., P-glycoprotein) which is one of the main causes of MDR. The tandem apoptosis strategy uses low level of chemodrug (in the nanomolar (nM) range) to eliminate MDR cancer cells. We further demonstrate that apoptosis of MDR cancer cells can be achieved in a spatially selective manner with single-cell level precision. Our study indicates that nanoscale tandem activation of convergent signaling pathways is a new platform concept to overcome MDR with high efficacy and specificity.

Controlled lateral quantum confinement in single-layer transition-metal chalcogenides (TMCs) can potentially combine the unique properties of two-dimensional (2D) exciton with the size-tunability of exciton energy, creating the single-layer quantum dots (SQDs) of 2D TMC materials. However, exploring such opportunities has been challenging due to the limited ability to produce well-defined SQDs with sufficiently high quality and size control, in conjunction with the commonly observed inconsistency in the optical properties. Here, we report an effective method to synthesize high-quality and size-controlled SQDs of WSe2 via multilayer quantum dots (MQDs) precursors, which enables grasping a clear picture of the role of lateral confinement on the optical properties of the 2D exciton. From the single-particle optical spectra and polarization anisotropy of WSe2 SQDs of varying sizes in addition to their ensemble data, we reveal how the properties of 2D exciton in single-layer TMCs evolve with increasing lateral...

Sensors that detect specific molecules of interest in a living organism can be useful tools for studying biological functions and diseases. Here, we provide a protocol for the construction of nanosensors that can noninvasively detect biologically important targets with magnetic resonance imaging (MRI). The key operating principle of these sensors is magnetic resonance tuning (MRET), a distance-dependent phenomenon occurring between a superparamagnetic quencher and a paramagnetic enhancer. The change in distance between the two magnetic components modulates the longitudinal (T1) relaxivity of the enhancer. In this MRET sensor, distance variation is achieved by interactive linkers that undergo binding, cleavage, or folding/unfolding upon their interaction with target molecules. By the modular incorporation of suitable linkers, the MRET sensor can be applied to a wide range of targets. We showcase three examples of MRET sensors for enzymes, nucleic acid sequences, and pH. This protocol comprises three stages: (i) chemical synthesis and surface modification of the quencher, (ii) conjugation with interactive linkers and enhancers, and (iii) MRI sensing of biological targets. The entire procedure takes up to 3 d. This protocol describes the synthesis of magnetic resonance tuning (MRET) sensors. The sensors consist of two magnetic components separated by a linker and can be modularly designed for targets such as enzymes, nucleic acid sequences, and pH values.

Achieving a molecular level understanding of chemical reactions on the surface of solid-state nanomaterials is important, but challenging. For example, the fully saturated basal plane is believed to be practically inert and its surface chemistry has been poorly explored, while two-dimensional (2D) layered transition-metal chalcogenides (TMCs) display unique reactivities due to their unusual anisotropic nature, where the edges consisting of unsaturated metals and chalcogens are sites for key chemical reactions. Herein, we report the use of Lewis acids/bases to elucidate the chemical reactivity of the basal plane in 2D layered TMCs. Electrophilic addition by Lewis acids (i.e., AlCl3) selectively onto sulfides in the basal plane followed by transmetalation and subsequent etching affords nanopores where such chemical activations are initiated and propagated from the localized positions of the basal plane. This new method of surface modification is generally applicable not only to various chemical compositions...