Naijia Liu

Human neural organoids are essential platforms for fundamental and applied research due partly to their complex, three-dimensional neuronal circuit geometries. Standard and recently developed neural interface technologies have shortcomings in their ability to electrically characterize and control neural activity in these systems, owing to their limited accessibility to neuron populations and microelectrode densities. Here we report a shape-matched, soft, three-dimensional mesoscale framework with nearly full surface coverage to neural organoids that supports high channel count interfaces for precision electrophysiology and programmed electrical stimulation. The neural interface is designed via inverse modelling techniques and self-assembles three-dimensionally around the organoids. Three-dimensional reconstruction of neural activities allows high-resolution spatial electrophysiology to reveal network-level characteristics in neural organoids. The porous framework offers options for simultaneous fluorescence imaging, localized optogenetic neuromodulation, longitudinal monitoring, pharmacological evaluations and modelling of neural disease phenotypes, demonstrating broad applicability for studies of human-derived cortical and spinal organoids.

Neural organoids are emerging as advanced three-dimensional (3D) in vitro models for recapitulating human development and pathology, but they lack dedicated mass-transport pathways that perfuse interior regions, limiting control over solute concentrations in deep tissues. Microfluidic technologies hold promise for intra-organoid delivery, yet creating high-resolution 3D transport architectures spanning arteriole-to-venule scales while integrating them with minimal disruption to morphogenesis remains challenging. Here, we introduce a multiscale 3D microfluidic delivery platform that embeds lithographically defined, flexible, thread-like microchannels into organoids during growth. The nanoporous interface along the embedded microchannels enables controlled diffusive transport of biomolecules into localized regions with ~100 um spatial resolution and to depths of ~400 um from the organoid center, with minute-scale temporal precision, as demonstrated with dyes, morphogens, and MRI contrast agents. Delivery of growth factor–supplemented media leads to reduced apoptosis near the microchannels and improved neural tissue integrity. This platform offers a robust means to interrogate deep, site-specific microenvironments and to advance studies of organoid viability, structural organization, and functional maturation.

Temporary pacemakers are essential for the care of patients with short-lived bradycardia in post-operative and other settings^1,2,3,4. Conventional devices require invasive open-heart surgery or less invasive endovascular surgery, both of which are challenging for paediatric and adult patients^5,6,7,8. Other complications^9,10,11 include risks of infections, lacerations and perforations of the myocardium, and of displacements of external power supplies and control systems. Here we introduce a millimetre-scale bioresorbable optoelectronic system with an onboard power supply and a wireless, optical control mechanism with generalized capabilities in electrotherapy and specific application opportunities in temporary cardiac pacing. The extremely small sizes of these devices enable minimally invasive implantation, including percutaneous injection and endovascular delivery. Experimental studies demonstrate effective pacing in mouse, rat, porcine, canine and human cardiac models at both single-site and multi-site locations. Pairing with a skin-interfaced wireless device allows autonomous, closed-loop operation upon detection of arrhythmias. Further work illustrates opportunities in combining these miniaturized devices with other medical implants, with an example of arrays of pacemakers for individual or collective use on the frames of transcatheter aortic valve replacement systems, to provide unique solutions that address risks for atrioventricular block following surgeries. This base technology can be readily adapted for a broad range of additional applications in electrotherapy, such as nerve and bone regeneration, wound therapy and pain management.

Despite the importance of atomic diffusion in controlling high temperature deformation, it remains difficult to generally determine diffusion flux through alloys. We present thermomechanical nanomolding, where a nanomold is filled by the alloy’s diffusion flux under a stress gradient, to determine the flux diffusing through an alloy’s microstructure. This flux is collected in the nanomold forming nanorods. Length and composition analyses of the formed nanorods allow us to determine rate and composition of the flux, and further allow estimation of the constituents’ diffusivities in this flux. We verify this technique on metals and simple alloys, and then reveal diffusive flux in general alloys. Notably, for alloys that can access a eutectic composition in their alloy system, the flux’s composition is that of the eutectic, which can be very different from the alloy’s nominal composition. Moreover, the flux’s overall diffusivity is greatly enhanced. This, so far unknown, eutectic mechanism is present in the majority of multicomponent alloys. These insights into diffusion flux in alloys can be used to guide the development of alloys with particularly low diffusivity or particularly high diffusivity. More generally, the presented method provides a novel toolbox to reveal the rich underlying diffusion-controlled mechanisms of deformation of alloys in general.

Monitoring homeostasis is an essential aspect of obtaining pathophysiological insights for treating patients. Accurate, timely assessments of homeostatic dysregulation in deep tissues typically require expensive imaging techniques or invasive biopsies. We introduce a bioresorbable shape-adaptive materials structure that enables real-time monitoring of deep-tissue homeostasis using conventional ultrasound instruments. Collections of small bioresorbable metal disks distributed within thin, pH-responsive hydrogels, deployed by surgical implantation or syringe injection, allow ultrasound-based measurements of spatiotemporal changes in pH for early assessments of anastomotic leaks after gastrointestinal surgeries, and their bioresorption after a recovery period eliminates the need for surgical extraction. Demonstrations in small and large animal models illustrate capabilities in monitoring leakage from the small intestine, the stomach, and the pancreas.

The underlying atomistic mechanism of deformation is a central problem in mechanics and materials science. Whereas deformation of crystalline metals is fundamentally understood, the understanding of deformation of amorphous metals lacks behind, particularly identifying the involved temporal and spatial scales. Here, we reveal that at small scales the size-dependent deformation behavior of amorphous metals significantly deviates from homogeneous flow, exhibiting increasing deformation rate with reducing size and gradually shifted composition. This transition suggests the deformation mechanism changes from collective atomic transport by viscous flow to individual atomic transport through interface diffusion. The critical length scale of the transition is temperature dependent, exhibiting a maximum at the glass transition. While viscous flow does not discriminate among alloy constituents, diffusion does and the constituent element with higher diffusivity deforms faster. Our findings yield insights into nano-mechanics and glass physics and may suggest alternative processing methods to epitaxially grow metallic glasses.

The understanding and quantification of plasticity in crystalline metals, which has led to their widespread and effective usage as a structural material, is lacking in metallic glasses (MGs). Here, we introduce such a framework for plasticity. This very practical framework is based on a MGs’ ability to support stable shear band growth, quantified in a stress gradient, , which we measure and calculate for a range of MGs. Whether a MG deforms plastically prior to fracture or only elastic in an application is determined by the comparison between and the applied stress field gradient, ∇𝜎app; if ∇𝜎US>∇𝜎app; if ∇𝜎US VS ∇𝜎app, the MG can only deform elastic prior to fracture, if ∇𝜎US<∇𝜎app, the MG can plastically deform, and ∇𝜎app―∇𝜎US indicates the magnitude of plasticity. This framework can explain observed plastic properties of MGs and their apparent contradicting brittle and tough characteristics. Looking forward, proposed framework provides first MG specific constitutive relation to quantitatively model their plastic behavior in any application.