Nature Biomedical Engineering最新文献

Minimally invasive neural interfaces can be used to diagnose, manage and treat many disorders, with reduced risks of surgical complications. However, endovascular probes lack access to key cortical, subcortical and spinal targets, and are not typically explantable after endothelialization. Here we report the development and testing, in sheep, of endocisternal neural interfaces that approach brain and spinal cord targets through inner and outer spaces filled with cerebrospinal fluid. Thus, the interfaces gain access to the entire brain convexity, to deep brain structures within the ventricles and to the spinal cord from the spinal subarachnoid space. We combined an endocisternal neural interface with wireless miniature magnetoelectrically powered bioelectronics so that it can be freely navigated percutaneously from the spinal space to the cranial subarachnoid space, and from the cranial subarachnoid space to the ventricles. In sheep, we show recording and stimulation functions, as well as repositioning of the flexible electrodes and explantation of the interface after chronic implantation. Minimally invasive endocisternal bioelectronics may enable chronic and transient therapies, particularly for stroke rehabilitation and epilepsy monitoring.

By monitoring brain neural signals, neural recorders allow for the study of neurological mechanisms underlying specific behavioural and cognitive states. However, the large brain volumes of non-human primates and their extensive range of uncontrolled movements and inherent wildness make it difficult to carry out covert and long-term recording and analysis of deep-brain neural signals. Here we report the development and performance of a stealthy neural recorder for the study of naturalistic behaviours in non-human primates. The neural recorder includes a fully implantable wireless and battery-free module for the recording of local field potentials and accelerometry data in real time, a flexible 32-electrode neural probe with a resorbable insertion shuttle, and a repeater coil-based wireless-power-transfer system operating at the body scale. We used the device to record neurobehavioural data for over 1 month in a freely moving monkey and leveraged the recorded data to train an artificial intelligence model for the classification of the animals’ eating behaviours.

Protein–protein interactions (PPIs) regulate signalling pathways and cell phenotypes, and the visualization of spatially resolved dynamics of PPIs would thus shed light on the activation and crosstalk of signalling networks. Here we report a method that leverages a sequential proximity ligation assay for the multiplexed profiling of PPIs with up to 47 proteins involved in multisignalling crosstalk pathways. We applied the method, followed by conventional immunofluorescence, to cell cultures and tissues of non-small-cell lung cancers with a mutated epidermal growth-factor receptor to determine the co-localization of PPIs in subcellular volumes and to reconstruct changes in the subcellular distributions of PPIs in response to perturbations by the tyrosine kinase inhibitor osimertinib. We also show that a graph convolutional network encoding spatially resolved PPIs can accurately predict the cell-treatment status of single cells. Multiplexed proximity ligation assays aided by graph-based deep learning can provide insights into the subcellular organization of PPIs towards the design of drugs for targeting the protein interactome.

Low sensitivity, photobleaching, high-power excitation and long acquisition times constrain the utility of afterglow luminescence. Here we report the design and imaging performance of nanoparticles made of electron-rich trianthracene derivatives that, on excitation by room light at ultralow power (58 μW cm^–2), emit afterglow luminescence at ~500 times those of commonly used organic afterglow nanoparticles. The nanoparticles’ ultrabright afterglow allowed for deep-tissue imaging (up to 6 cm), for ultrafast afterglow imaging (at short acquisition times down to 0.01 s) of naturally behaving mice with negligible photobleaching, even after re-excitation for over 15 cycles, and for the accurate visualization of subcutaneous and orthotopic tumours and of plaque in carotid arteries. We also show that an afterglow nanoparticle that is activated only in the presence of granzyme B allowed for the tracking of granzyme-B activity in the context of therapeutic monitoring. The high sensitivity and negligible photobleaching of the organic afterglow nanoparticles offer advantages for real-time in vivo monitoring of physiopathological processes.