Zhe Li

Repairing abnormal vessels in the complex fluidic and biological environment of blood remains challenging. Current approaches, such as non‐adhesive polymeric sealants or vessel coiling, have unsatisfactory outcomes. Here, we present an injectable magnetoactive adhesive hydrogel (iMAH) for vascular repair in the challenging blood environment. Designed with biocompatible functional components, including the superparamagnetic component, a bio‐inspired tissue adhesive, and quick‐crosslinking agents, the catheter‐deployable iMAH can be magnetically guided to a targeted site, quickly crosslink within approximately 2 s, and strongly adhere to the vessel surface in dynamic conditions with circulating and pressurized blood. Moreover, magnetic actuation enables targeted gel deployment and can drive the iMAH into a narrow and confined space, squeezing out interfacial fluid to facilitate high‐strength tissue adhesion, as systematically investigated in vitro. Magnetically controlled delivery of iMAH for vascular repair has been demonstrated in a large‐animal beagle dog model; branching lumbar arteries from the abdominal aorta, mimicking the opening of a ruptured artery, were successfully embolized under magnetic guidance using a 5‐axis magnetic vascular robot. With these demonstrated features, magnetically controlled delivery of injectable magnetoactive adhesive hydrogel provides a promising solution for vascular repair such as sealing ruptured vessels or embolizing abnormal arteries in the challenging blood environment.

Intracranial pressure (ICP) is an important indicator in the management of brain disease. The gold‐standard method for ICP monitoring via external ventricular drainage is invasive, and wired pressure‐measuring techniques are not suitable for convenient ICP monitoring; meanwhile, existing wireless ICP measurement methods typically require invasive insertion of a thick cannula into the ventricle or implantation of an epidural or subdural pressure sensor. This study presents a method of minimally invasive and wireless ICP monitoring via micro‐hole intervention. First, assisted by the ultrasonic vibration‐assisted micro‐hole craniotomy, a high‐quality micro‐hole is generated on the skull, providing a micro‐tunnel to access the brain. Next, the dura mater beneath the micro‐hole in the skull is precisely ablated using the cyclic low‐power electroablation method. Furthermore, a miniaturized wireless capacitive pressure sensor has been developed; the pressure sensor, designed with a micro‐cannula of the same diameter as the micro‐hole in the skull, can be conveniently implanted to access the cerebrospinal fluid for ICP monitoring. The effectiveness of this method has been demonstrated in vivo on rabbits. Micro‐hole craniotomy and micro‐hole dura electroablation, as well as the miniaturized pressure sensor, collectively enable wireless ICP monitoring via micro‐hole intervention, offering great convenience with minimal invasiveness.

Brain's unique anatomical structure and physiological environment make it difficult to deliver therapeutic agents such as drug or light to a focal volume in brain for disease treatment. Physically targeting a fine structure in brain with a micro‐neural probe is an effective solution. Here, we present a hybrid miniaturized neural probe designed with micro‐fluidic channel(s) for drug delivery, micro‐electrode(s) for neural sensing and an optical fiber for optical‐related treatment. These functional components are integrated in a micro‐cannula (diameter <300 µm) with modular design and fabrication properties which can be conveniently adjusted for diverse applications. In vitro and in vivo tests confirm that this probe can precisely deliver drug to a focal volume in brain bypassing the blood brain barrier, and on‐site neural sensing can be achieved with the integrated neural electrode. Leveraging near infrared light’s scattering properties in brain, we demonstrate in vivo with rat glioblastoma model that this hybrid neural probe can be a platform for photothermal treatment of brain tumor. With these merits, the hybrid miniaturized neural probe will be an effective tool with great translational potentials for minimally invasive neural intervention such as drug delivery or combination treatment of brain diseases.

Soft electromagnetic devices have great potential in soft robotics and biomedical applications. However, existing soft-magneto-electrical devices would have limited hybrid functions and suffer from damaging stress concentrations, delamination or material leakage. Here, we report a hybrid magnetic-mechanical-electrical (MME) core-sheath fiber to overcome these challenges. Assisted by the coaxial printing method, the MME fiber can be printed into complex 2D/3D MME structures with integrated magnetoactive and conductive properties, further enabling hybrid functions including programmable magnetization, somatosensory, and magnetic actuation along with simultaneous wireless energy transfer. To demonstrate the great potential of MME devices, precise and minimally invasive electro-ablation was performed with a flexible MME catheter with magnetic control, hybrid actuation-sensing was performed by a durable somatosensory MME gripper, and hybrid wireless energy transmission and magnetic actuation were demonstrated by an untethered soft MME robot. Our work thus provides a material design strategy for soft electromagnetic devices with unexplored hybrid functions.

Early diagnosis of Alzheimer’s disease (AD) is critical for preventing disease progression, however, the diagnosis of AD remains challenging for most patients due to limitations of current sensing technologies. A common pathological feature found in AD-affected brains is the accumulation of Amyloid-β (Aβ) polypeptides, which lead to neurofibrillary tangles and neuroinflammatory plaques. Here, we developed a portable ultrasensitive FET biosensor chip based on a self-assembled nanoporous membrane for ultrasensitive detection of Aβ protein in complex environments. The microscale semiconductor channel was covered with a self-assembled organic nanoporous membrane modified by antibody molecules to pick up and amplify the Aβ protein signal. The nanoporous structure helps protect the sensitive channel from non-target proteins and improves its stability since no chemical functionalization process involved, largely reduces background noise of the sensing platform. When a bio-gated target is captured, the doping state of the polymer bulk could be tuned and amplified the strength of the weak signal, achieving ultrasensitive detecting performance (enabling the device to detect target protein less than 1 fg/ml in 1 µl sample). Moreover, the device simplifies the circuit connection by integrating all the connections on a 2 cm × 2 cm chip, avoiding expensive and complex manufacturing processes, and makes it usable for portable prognosis. We believe that this ultrasensitive, portable, low-cost Aβ sensor chip shows the great potential in the early diagnosis of AD and large-scale population screening applications.

Recent advances in miniaturized neural implants for precise, controllable and minimally invasive drug delivery in the brain are reviewed to provide a comprehensive landscape of the technologies and devices for drug delivery in the brain.