Dynamics of plosive consonants via imaging, computations, and soft electronics.

A quantitative understanding of the coupled dynamics of flow and particles in aerosol and droplet transmission associated with speech remains elusive. Here, we summarize an effort that integrates insights into flow-particle dynamics induced by the production plosive sounds during speech with skin-integrated electronic systems for monitoring the production of these sounds. In particular, we uncover diffusive and ballistic regimes separated by a threshold particle size and characterize the Lagrangian acceleration and pair dispersion. Lagrangian dynamics of the particles in the diffusive regime exhibit features of isotropic turbulence. These fundamental findings highlight the value in skin-interfaced wireless sensors for continuously measuring critical speech patterns in clinical settings, work environments, and the home, based on unique neck biomechanics associated with the generation of plosive sounds. We introduce a wireless, soft device that captures these motions to enable detection of plosive sounds in multiple languages through a convolutional neural network approach. This work spans fundamental flow-particle physics to soft electronic technology, with implications in monitoring and studying critical speech patterns associated with aerosol and droplet transmissions relevant to the spread of infectious diseases.

Soft shape-programmable surfaces by fast electromagnetic actuation of liquid metal networks.

Low modulus materials that can shape-morph into different three-dimensional (3D) configurations in response to external stimuli have wide-ranging applications in flexible/stretchable electronics, surgical instruments, soft machines and soft robotics. This paper reports a shape-programmable system that exploits liquid metal microfluidic networks embedded in an elastomer matrix, with electromagnetic forms of actuation, to achieve a unique set of properties. Specifically, this materials structure is capable of fast, continuous morphing into a diverse set of continuous, complex 3D surfaces starting from a two-dimensional (2D) planar configuration, with fully reversible operation. Computational, multi-physics modeling methods and advanced 3D imaging techniques enable rapid, real-time transformations between target shapes. The liquid-solid phase transition of the liquid metal allows for shape fixation and reprogramming on demand. An unusual vibration insensitive, dynamic 3D display screen serves as an application example of this type of morphable surface.

Iodine-Rich Nanoadjuvants for CT Imaging-Guided Photodynamic Immunotherapy of Breast Cancer.

Immunotherapy, which stimulates the body's own immune system to kill cancer cells, has shown great promise in the field of cancer therapy. However, the uncontrolled biodistribution of immunotherapeutic drugs may cause severe side effects. Herein, we report an iodine-rich nanoadjuvant (INA) for photo-immunotherapy. INA is prepared by encapsulating a toll-like receptor 7 agonist (R837) and a photosensitizer (phthalocyanine) into an iodine-rich amphiphilic copolymer PEG-PHEMA-I. By virtue of the enhanced permeation and retention (EPR) effect, INA can effectively accumulate into the tumor site. Under light irradiation, photodynamic therapy (PDT) triggered by INA will induce immunogenic cell death (ICD) in the tumor region to trigger the release of immune-associated cytokines. Such a process may further induce the maturation of dendritic cells which will be accelerated by R837, leading to the proliferation of effector T cells for immunotherapy. The photo-immunotherapy mediated by INA shows good anticancer efficacy both in vitro and in vivo. Meanwhile, INA is also a CT contrast agent owing to its high density of iodine, which can successfully illuminate tumors by CT imaging. Thus, our study develops a light-triggered nanoadjuvant for CT imaging-guided enhanced photo-immunotherapy.

A dynamically reprogrammable surface with self-evolving shape morphing.

Dynamic shape-morphing soft materials systems are ubiquitous in living organisms; they are also of rapidly increasing relevance to emerging technologies in soft machines1-3, flexible electronics4,5 and smart medicines6. Soft matter equipped with responsive components can switch between designed shapes or structures, but cannot support the types of dynamic morphing capabilities needed to reproduce natural, continuous processes of interest for many applications7-24. Challenges lie in the development of schemes to reprogram target shapes after fabrication, especially when complexities associated with the operating physics and disturbances from the environment can stop the use of deterministic theoretical models to guide inverse design and control strategies25-30. Here we present a mechanical metasurface constructed from a matrix of filamentary metal traces, driven by reprogrammable, distributed Lorentz forces that follow from the passage of electrical currents in the presence of a static magnetic field. The resulting system demonstrates complex, dynamic morphing capabilities with response times within 0.1 second. Implementing an in situ stereo-imaging feedback strategy with a digitally controlled actuation scheme guided by an optimization algorithm yields surfaces that can follow a self-evolving inverse design to morph into a wide range of three-dimensional target shapes with high precision, including an ability to morph against extrinsic or intrinsic perturbations. These concepts support a data-driven approach to the design of dynamic soft matter, with many unique characteristics.

Capsaicin-Decorated Semiconducting Polymer Nanoparticles for Light-Controlled Calcium-Overload/Photodynamic Combination Therapy.

Calcium-overload cancer therapy has gained more and more attention owing to its good therapeutic efficacy with low side effect. However, conventional calcium-overload therapy is achieved by introducing an additional calcium element into the tumor site by nanomedicines, which may also lead to the calcium-overload of normal organs, causing an undesirable side effect. To address such issues, capsaicin-decorated semiconducting polymer nanoparticles (CSPN) are designed to modulate the calcium ion channel of cancer cells for calcium-overload cancer therapy without adding an additional calcium element. CSPN is composed of a near-infrared (NIR) absorbing semiconducting polymer (SP) PCPDTBT and a capsaicin-conjugated amphiphilic copolymer, PEG-PHEMA-Cap. Under NIR laser irradiation, PCPDTBT can generate singlet oxygen (1 O2 ), which not only triggers the release of capsaicin, but also induces photodynamic therapy (PDT). The released capsaicin can further activate transient receptor potential cation channel subfamily V member 1 (TRPV1) of U373 cancer cells, leading to an influx of calcium ions into cells. In addition, the intense NIR-II fluorescence signal of CSPN makes it suitable for tumor imaging. Thus, this study develops a tumor specific nanotheranostic system for NIR-II fluorescence imaging-guided calcium-overload/PDT combination therapy.

Semiconducting polymer nanoparticles for NIR-II fluorescence imaging-guided photothermal/thermodynamic combination therapy.

Photothermal therapy is a promising phototherapeutic modality that has been widely studied in cancer therapy. However, because of the influence of heat shock protein (HSP), the therapeutic efficacy of photothermal therapy (PTT) is significantly suppressed. To improve the therapeutic efficacy, different tumor-specific therapeutic modalities have been chosen to combine with PTT. However, most of them rely on endogenous stimuli to trigger combination therapy, which may suffer from the issue of incomplete activation. Herein, we develop a PTT/thermodynamic combination therapeutic nanosystem whose therapeutic process is controlled by an external stimulus, near-infrared (NIR) light. The nanosystem (ADPPTN) is composed of a second NIR (NIR-II) fluorescent semiconducting polymer (SP) (DPPT) as the core, and a carboxyl group-decorated amphiphilic copolymer (PSMA-PEG) as the shell with an azo-containing compound (AIPH) loaded via electrostatic interaction. Under 808 nm laser irradiation, DPPT can generate heat to conduct PTT, while the elevated temperature may further trigger the release of AIPH radicals, conducting thermodynamic therapy (TDT). In addition, the NIR-II fluorescence signal emitted from DPPT can light the tumor. Compared with the nanoparticles without AIPH (DPPTN), ADPPTN has better anticancer efficacy under laser irradiation both in vitro and in vivo. Thus, our study provides an NIR-II fluorescence imaging-guided PTT/TDT combination therapeutic nanosystem for efficient cancer theranostics.

Peptide-based semiconducting polymer nanoparticles for osteosarcoma-targeted NIR-II fluorescence/NIR-I photoacoustic dual-model imaging and photothermal/photodynamic therapies.

BACKGROUND: The overall survival rate of osteosarcoma (OS) patients has not been improved for 30 years, and the diagnosis and treatment of OS is still a critical issue. To improve OS treatment and prognosis, novel kinds of theranostic modalities are required. Molecular optical imaging and phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), are promising strategies for cancer theranostics that exhibit high imaging sensitivity as well as favorable therapeutic efficacy with minimal side effect. In this study, semiconducting polymer nanoparticles (SPN-PT) for OS-targeted PTT/PDT are designed and prepared, using a semiconducting polymer (PCPDTBT), providing fluorescent emission in the second near-infrared window (NIR-II, 1000 - 1700 nm) and photoacoustic (PA) signal in the first near-infrared window (NIR-I, 650 - 900 nm), served as the photosensitizer, and a polyethylene glycolylated (PEGylated) peptide PT, providing targeting ability to OS. RESULTS: The results showed that SPN-PT nanoparticles significantly accelerated OS-specific cellular uptake and enhanced therapeutic efficiency of PTT and PDT effects in OS cell lines and xenograft mouse models. SPN-PT carried out significant anti-tumor activities against OS both in vitro and in vivo. CONCLUSIONS: Peptide-based semiconducting polymer nanoparticles permit efficient NIR-II fluorescence/NIR-I PA dual-modal imaging and targeted PTT/PDT for OS.

A Wireless Near-Infrared Spectroscopy Device for Flap Monitoring: Proof of Concept in a Porcine Musculocutaneous Flap Model.

BACKGROUND: Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are highly sensitive for detecting malperfusion. However, the clinical utility and user experience are limited by the wired connection between the sensor and bedside console. This wire leads to instability of the flap-sensor interface and may cause false alarms. METHODS: We present a novel wearable wireless NIRS sensor for continuous fasciocutaneous free flap monitoring. This waterproof silicone-encapsulated Bluetooth-enabled device contains two light-emitting diodes and two photodetectors in addition to a battery sufficient for 5 days of uninterrupted function. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. RESULTS: Devices were tested in four flaps using three animals. Both devices produced very similar tissue oxygen saturation (StO2) tracings throughout the vascular clamping events, with obvious and parallel changes occurring on arterial clamping, arterial release, venous clamping, and venous release. Small interdevice variations in absolute StO2 value readings and magnitude of change were observed. The normalized cross-correlation at zero lag describing correspondence between the novel NIRS and T.Ox devices was >0.99 in each trial. CONCLUSION: The wireless NIRS flap monitor is capable of detecting StO2 changes resultant from arterial vascular occlusive events. In this porcine flap model, the functionality of this novel sensor closely mirrored that of the T.Ox wired platform. This device is waterproof, highly adhesive, skin conforming, and has sufficient battery life to function for 5 days. Clinical testing is necessary to determine if this wireless functionality translates into fewer false-positive alarms and a better user experience.

Differential cardiopulmonary monitoring system for artifact-canceled physiological tracking of athletes, workers, and COVID-19 patients.

Soft, skin-integrated electronic sensors can provide continuous measurements of diverse physiological parameters, with broad relevance to the future of human health care. Motion artifacts can, however, corrupt the recorded signals, particularly those associated with mechanical signatures of cardiopulmonary processes. Design strategies introduced here address this limitation through differential operation of a matched, time-synchronized pair of high-bandwidth accelerometers located on parts of the anatomy that exhibit strong spatial gradients in motion characteristics. When mounted at a location that spans the suprasternal notch and the sternal manubrium, these dual-sensing devices allow measurements of heart rate and sounds, respiratory activities, body temperature, body orientation, and activity level, along with swallowing, coughing, talking, and related processes, without sensitivity to ambient conditions during routine daily activities, vigorous exercises, intense manual labor, and even swimming. Deployments on patients with COVID-19 allow clinical-grade ambulatory monitoring of the key symptoms of the disease even during rehabilitation protocols.

A skin-conformable wireless sensor to objectively quantify symptoms of pruritus.

Itch is a common clinical symptom and major driver of disease-related morbidity across a wide range of medical conditions. A substantial unmet need is for objective, accurate measurements of itch. In this article, we present a noninvasive technology to objectively quantify scratching behavior via a soft, flexible, and wireless sensor that captures the acousto-mechanic signatures of scratching from the dorsum of the hand. A machine learning algorithm validated on data collected from healthy subjects (n = 10) indicates excellent performance relative to smartwatch-based approaches. Clinical validation in a cohort of predominately pediatric patients (n = 11) with moderate to severe atopic dermatitis included 46 sleep-nights totaling 378.4 hours. The data indicate an accuracy of 99.0% (84.3% sensitivity, 99.3% specificity) against visual observation. This work suggests broad capabilities relevant to applications ranging from assessing the efficacy of drugs for conditions that cause itch to monitoring disease severity and treatment response.

Automated, multiparametric monitoring of respiratory biomarkers and vital signs in clinical and home settings for COVID-19 patients.

Capabilities in continuous monitoring of key physiological parameters of disease have never been more important than in the context of the global COVID-19 pandemic. Soft, skin-mounted electronics that incorporate high-bandwidth, miniaturized motion sensors enable digital, wireless measurements of mechanoacoustic (MA) signatures of both core vital signs (heart rate, respiratory rate, and temperature) and underexplored biomarkers (coughing count) with high fidelity and immunity to ambient noises. This paper summarizes an effort that integrates such MA sensors with a cloud data infrastructure and a set of analytics approaches based on digital filtering and convolutional neural networks for monitoring of COVID-19 infections in sick and healthy individuals in the hospital and the home. Unique features are in quantitative measurements of coughing and other vocal events, as indicators of both disease and infectiousness. Systematic imaging studies demonstrate correlations between the time and intensity of coughing, speaking, and laughing and the total droplet production, as an approximate indicator of the probability for disease spread. The sensors, deployed on COVID-19 patients along with healthy controls in both inpatient and home settings, record coughing frequency and intensity continuously, along with a collection of other biometrics. The results indicate a decaying trend of coughing frequency and intensity through the course of disease recovery, but with wide variations across patient populations. The methodology creates opportunities to study patterns in biometrics across individuals and among different demographic groups.

Designing Mechanical Metamaterials with Kirigami-Inspired, Hierarchical Constructions for Giant Positive and Negative Thermal Expansion.

Advanced mechanical metamaterials with unusual thermal expansion properties represent an area of growing interest, due to their promising potential for use in a broad range of areas. In spite of previous work on metamaterials with large or ultralow coefficient of thermal expansion (CTE), achieving a broad range of CTE values with access to large thermally induced dimensional changes in structures with high filling ratios remains a key challenge. Here, design concepts and fabrication strategies for a kirigami-inspired class of 2D hierarchical metamaterials that can effectively convert the thermal mismatch between two closely packed constituent materials into giant levels of biaxial/uniaxial thermal expansion/shrinkage are presented. At large filling ratios (>50%), these systems offer not only unprecedented negative and positive biaxial CTE (i.e., -5950 and 10 710 ppm K-1 ), but also large biaxial thermal expansion properties (e.g., > 21% for 20 K temperature increase). Theoretical modeling of thermal deformations provides a clear understanding of the microstructure-property relationships and serves as a basis for design choices for desired CTE values. An Ashby plot of the CTE versus density serves as a quantitative comparison of the hierarchical metamaterials presented here to previously reported systems, indicating the capability for substantially enlarging the accessible range of CTE.

Recent Advances in Crosslinked Nanogel for Multimodal Imaging and Cancer Therapy.

Nanomaterials have been widely applied in the field of cancer imaging and therapy. However, conventional nanoparticles including micelles and liposomes may suffer the issue of dissociation in the circulation. In contrast, crosslinked nanogels the structures of which are covalently crosslinked have better physiological stability than micelles and liposomes, making them more suitable for cancer theranostics. In this review, we summarize recent advances in crosslinked nanogels for cancer imaging and therapy. The applications of nanogels in drug and gene delivery as well as development of novel cancer therapeutic methods are first introduced, followed by the introduction of applications in optical and multimodal imaging, and imaging-guided cancer therapy. The conclusion and future direction in this field are discussed at the end of this review.

Mechano-acoustic sensing of physiological processes and body motions via a soft wireless device placed at the suprasternal notch.

Skin-mounted soft electronics that incorporate high-bandwidth triaxial accelerometers can capture broad classes of physiologically relevant information, including mechano-acoustic signatures of underlying body processes (such as those measured by a stethoscope) and precision kinematics of core-body motions. Here, we describe a wireless device designed to be conformally placed on the suprasternal notch for the continuous measurement of mechano-acoustic signals, from subtle vibrations of the skin at accelerations of around 10-3 m s-2 to large motions of the entire body at about 10 m s-2, and at frequencies up to around 800 Hz. Because the measurements are a complex superposition of signals that arise from locomotion, body orientation, swallowing, respiration, cardiac activity, vocal-fold vibrations and other sources, we exploited frequency-domain analysis and machine learning to obtain-from human subjects during natural daily activities and exercise-real-time recordings of heart rate, respiration rate, energy intensity and other essential vital signs, as well as talking time and cadence, swallow counts and patterns, and other unconventional biomarkers. We also used the device in sleep laboratories and validated the measurements using polysomnography.

2D Mechanical Metamaterials with Widely Tunable Unusual Modes of Thermal Expansion.

Most natural materials expand uniformly in all directions upon heating. Artificial, engineered systems offer opportunities to tune thermal expansion properties in interesting ways. Previous reports exploit diverse design principles and fabrication techniques to achieve a negative or ultralow coefficient of thermal expansion, but very few demonstrate tunability over different behaviors. This work presents a collection of 2D material structures that exploit bimaterial serpentine lattices with micrometer feature sizes as the basis of a mechanical metamaterials system capable of supporting positive/negative, isotropic/anisotropic, and homogeneous/heterogeneous thermal expansion properties, with additional features in unusual shearing, bending, and gradient modes of thermal expansion. Control over the thermal expansion tensor achieved in this way provides a continuum-mechanics platform for advanced strain-field engineering, including examples of 2D metamaterials that transform into 3D surfaces upon heating. Integrated electrical and optical sources of thermal actuation provide capabilities for reversible shape reconfiguration with response times of less than 1 s, as the basis of dynamically responsive metamaterials.

Bioresorbable photonic devices for the spectroscopic characterization of physiological status and neural activity.

Capabilities in real-time monitoring of internal physiological processes could inform pharmacological drug-delivery schedules, surgical intervention procedures and the management of recovery and rehabilitation. Current methods rely on external imaging techniques or implantable sensors, without the ability to provide continuous information over clinically relevant timescales, and/or with requirements in surgical procedures with associated costs and risks. Here, we describe injectable classes of photonic devices, made entirely of materials that naturally resorb and undergo clearance from the body after a controlled operational lifetime, for the spectroscopic characterization of targeted tissues and biofluids. As an example application, we show that the devices can be used for the continuous monitoring of cerebral temperature, oxygenation and neural activity in freely moving mice. These types of devices should prove useful in fundamental studies of disease pathology, in neuroscience research, in surgical procedures and in monitoring of recovery from injury or illness.

Yield Precursor Dislocation Avalanches in Small Crystals: The Irreversibility Transition.

The transition from elastic to plastic deformation in crystalline metals shares history dependence and scale-invariant avalanche signature with other nonequilibrium systems under external loading such as colloidal suspensions. These other systems exhibit transitions with clear analogies to work hardening and yield stress, with many typically undergoing purely elastic behavior only after "training" through repeated cyclic loading; studies in these other systems show a power-law scaling of the hysteresis loop extent and of the training time as the peak load approaches a so-called reversible-to-irreversible transition (RIT). We discover here that deformation of small crystals shares these key characteristics: yielding and hysteresis in uniaxial compression experiments of single-crystalline Cu nano- and micropillars decay under repeated cyclic loading. The amplitude and decay time of the yield precursor avalanches diverge as the peak stress approaches failure stress for each pillar, with a power-law scaling virtually equivalent to RITs in other nonequilibrium systems.

Probing Microplasticity in Small-Scale FCC Crystals via Dynamic Mechanical Analysis.

In small-scale metallic systems, collective dislocation activity has been correlated with size effects in strength and with a steplike plastic response under uniaxial compression and tension. Yielding and plastic flow in these samples is often accompanied by the emergence of multiple dislocation avalanches. Dislocations might be active preyield, but their activity typically cannot be discerned because of the inherent instrumental noise in detecting equipment. We apply alternate current load perturbations via dynamic mechanical analysis during quasistatic uniaxial compression experiments on single crystalline Cu nanopillars with diameters of 500 nm and compute dynamic moduli at frequencies 0.1, 0.3, 1, and 10 Hz under progressively higher static loads until yielding. By tracking the collective aspects of the oscillatory stress-strain-time series in multiple samples, we observe an evolving dissipative component of the dislocation network response that signifies the transition from elastic behavior to dislocation avalanches in the globally preyield regime. We postulate that microplasticity, which is associated with the combination of dislocation avalanches and slow viscoplastic relaxations, is the cause of the dependency of dynamic modulus on the driving rate and the quasistatic stress. We construct a continuum mesoscopic dislocation dynamics model to compute the frequency response of stress over strain and obtain a consistent agreement with experimental observations. The results of our experiments and simulations present a pathway to discern and quantify correlated dislocation activity in the preyield regime of deforming crystals.

Exceptional Resilience of Small-Scale Au30Cu25Zn45 under Cyclic Stress-Induced Phase Transformation.

Shape memory alloys that produce and recover from large deformation driven by martensitic transformation are widely exploited in biomedical devices and microactuators. Generally their actuation work degrades significantly within first a few cycles and is reduced at smaller dimensions. Further, alloys exhibiting unprecedented reversibility have relatively small superelastic strain, 0.7%. These raise the questions of whether high reversibility is necessarily accompanied by small work and strain and whether high work and strain is necessarily diminished at small scale. Here we conclusively demonstrate that these are not true by showing that Au30Cu25Zn45 pillars exhibit 12 MJ m-3 work and 3.5% superelastic strain even after 100 000 phase transformation cycles. Our findings confirm that the lattice compatibility dominates the mechanical behavior of phase-changing materials at nano to micron scales and points a way for smart microactuators design having the mutual benefits of high actuation work and long lifetime.