Yuxiang Ma

Abstract Continuous imaging of cardiac functions is highly desirable for the assessment of long-term cardiovascular health, detection of acute cardiac dysfunction and clinical management of critically ill or surgical patients 1–4 . However, conventional non-invasive approaches to image the cardiac function cannot provide continuous measurements owing to device bulkiness 5–11 , and existing wearable cardiac devices can only capture signals on the skin 12–16 . Here we report a wearable ultrasonic device for continuous, real-time and direct cardiac function assessment. We introduce innovations in device design and material fabrication that improve the mechanical coupling between the device and human skin, allowing the left ventricle to be examined from different views during motion. We also develop a deep learning model that automatically extracts the left ventricular volume from the continuous image recording, yielding waveforms of key cardiac performance indices such as stroke volume, cardiac output and ejection fraction. This technology enables dynamic wearable monitoring of cardiac performance with substantially improved accuracy in various environments.

Uniform gold nanostars (Au NS) were conjugated with cyclic RGD (cRGD) and near infrared (NIR) fluorescence probe (MPA) or anti-cancer drug (DOX) to obtain multi-functional nanoconstructs, Au-cRGD-MPA and Au-cRGD-DOX respectively. The NIR contrast agent Au-cRGD-MPA was shown to have low cytotoxicity. Using tumor cells and tumor bearing mice, these imaging nanoparticles demonstrated favorable tumor-targeting capability mediated by RGD peptide binding to its over-expressed receptor on the tumor cells. The multi-therapeutic analogue, Au-cRGD-DOX, integrates targeting tumor, chemotherapy and photo-thermotherapy into a single system. The synergistic effect of photo-thermal therapy and chemotherapy was demonstrated in different tumor cell lines and in vivo using S180 tumor-bearing mouse models. The viability of MDA-MB-231 cells was only 40 % after incubation with Au-cRGD-DOX and irradiation with NIR light. Both tail vein and intratumoral injections showed Au-cRGD-DOX treated mice exhibiting the slowest tumor increase. These results indicate that the multifunctional nanoconstruct is a promising combined therapeutic agent for tumor-targeting treatment, with the potential to enhance the anti-cancer treatment outcomes.

Serial assessment of the biomechanical properties of tissues can be used to aid the early detection and management of pathophysiological conditions, to track the evolution of lesions and to evaluate the progress of rehabilitation. However, current methods are invasive, can be used only for short-term measurements, or have insufficient penetration depth or spatial resolution. Here we describe a stretchable ultrasonic array for performing serial non-invasive elastographic measurements of tissues up to 4 cm beneath the skin at a spatial resolution of 0.5 mm. The array conforms to human skin and acoustically couples with it, allowing for accurate elastographic imaging, which we validated via magnetic resonance elastography. We used the device to map three-dimensional distributions of the Young's modulus of tissues ex vivo, to detect microstructural damage in the muscles of volunteers before the onset of soreness and to monitor the dynamic recovery process of muscle injuries during physiotherapies. The technology may facilitate the diagnosis and treatment of diseases affecting tissue biomechanics.

Electronic patches, based on various mechanisms, allow continuous and noninvasive monitoring of biomolecules on the skin surface. However, to date, such devices are unable to sense biomolecules in deep tissues, which have a stronger and faster correlation with the human physiological status than those on the skin surface. Here, we demonstrate a photoacoustic patch for three-dimensional (3D) mapping of hemoglobin in deep tissues. This photoacoustic patch integrates an array of ultrasonic transducers and vertical-cavity surface-emitting laser (VCSEL) diodes on a common soft substrate. The high-power VCSEL diodes can generate laser pulses that penetrate >2 cm into biological tissues and activate hemoglobin molecules to generate acoustic waves, which can be collected by the transducers for 3D imaging of the hemoglobin with a high spatial resolution. Additionally, the photoacoustic signal amplitude and temperature have a linear relationship, which allows 3D mapping of core temperatures with high accuracy and fast response. With access to biomolecules in deep tissues, this technology adds unprecedented capabilities to wearable electronics and thus holds significant implications for various applications in both basic research and clinical practice.