Abstract
Microcatheters have enabled diverse minimally invasive endovascular operations and notable health benefits compared with open surgeries. However, with tortuous routes far from the arterial ...puncture site, the distal vascular regions remain challenging for safe catheter access. Therefore, we propose a wireless stent-shaped magnetic soft robot to be deployed, actively navigated, used for medical functions, and retrieved in the example M4 segment of the middle cerebral artery. We investigate shape-adaptively controlled locomotion in phantoms emulating the physiological conditions here, where the lumen diameter shrinks from 1.5 mm to 1 mm, the radius of curvature of the tortuous lumen gets as small as 3 mm, the lumen bifurcation angle goes up to 120
°
, and the pulsatile flow speed reaches up to 26 cm/s. The robot can also withstand the flow when the magnetic actuation is turned off. These locomotion capabilities are confirmed in porcine arteries ex vivo. Furthermore, variants of the robot could release the tissue plasminogen activator on-demand locally for thrombolysis and function as flow diverters, initiating promising therapies towards acute ischemic stroke, aneurysm, arteriovenous malformation, dural arteriovenous fistulas, and brain tumors. These functions should facilitate the robot’s usage in new distal endovascular operations.
Electrical stimulation is a fundamental tool in studying neural circuits, treating neurological diseases, and advancing regenerative medicine. Injectable, free-standing piezoelectric particle systems ...have emerged as non-genetic and wireless alternatives for electrode-based tethered stimulation systems. However, achieving cell-specific and high-frequency piezoelectric neural stimulation remains challenging due to high-intensity thresholds, non-specific diffusion, and internalization of particles. Here, we develop cell-sized 20 μm-diameter silica-based piezoelectric magnetic Janus microparticles (PEMPs), enabling clinically-relevant high-frequency neural stimulation of primary neurons under low-intensity focused ultrasound. Owing to its functionally anisotropic design, half of the PEMP acts as a piezoelectric electrode via conjugated barium titanate nanoparticles to induce electrical stimulation, while the nickel-gold nanofilm-coated magnetic half provides spatial and orientational control on neural stimulation via external uniform rotating magnetic fields. Furthermore, surface functionalization with targeting antibodies enables cell-specific binding/targeting and stimulation of dopaminergic neurons. Taking advantage of such functionalities, the PEMP design offers unique features towards wireless neural stimulation for minimally invasive treatment of neurological diseases.
Neural interfaces are the fundamental tools to understand the brain and cure many nervous-system diseases. For proper interfacing, seamless integration, efficient and safe digital-to-biological ...signal transduction, and long operational lifetime are required. Here, we devised a wireless optoelectronic pseudocapacitor converting the optical energy to safe capacitive currents by dissociating the photogenerated excitons in the photovoltaic unit and effectively routing the holes to the supercapacitor electrode and the pseudocapacitive electrode–electrolyte interfacial layer of PEDOT:PSS for reversible faradic reactions. The biointerface showed high peak capacitive currents of ∼3 mA·cm–2 with total charge injection of ∼1 μC·cm–2 at responsivity of 30 mA·W–1, generating high photovoltages over 400 mV for the main eye photoreception colors of blue, green, and red. Moreover, modification of PEDOT:PSS controls the charging/discharging phases leading to rapid capacitive photoresponse of 50 μs and effective membrane depolarization at the single-cell level. The neural interface has a device lifetime of over 1.5 years in the aqueous environment and showed stability without significant performance decrease after sterilization steps. Our results demonstrate that adopting the pseudocapacitance phenomenon on organic photovoltaics paves an ultraefficient, safe, and robust way toward communicating with biological systems.
Abstract Light activated modulation of neural activity is an emerging field for the basic investigation of neural systems and development of new therapeutic methods such as artificial retina. ...Colloidal inorganic nanocrystals have great potential for neural interfaces due to their adjustable optoelectronic properties via high-level structural, compositional, and size control. However, toxic heavy metal content (e.g., cadmium, mercury), electrochemical coupling to the cells and low photon-to-current efficiency limit their effective use. Here, we introduce the use of aluminum antimonide (AlSb) nanocrystals as the cell interfacing layer for capacitive neural stimulation in the blue spectrum. We demonstrate successful photostimulation of primary hippocampal neurons below ocular safety limits. In addition, our device shows high biocompatibility in vitro and passive accelerated ageing tests indicate a functional lifetime over 3 years showing their feasible use for chronic implants. We demonstrate that nanocrystal biointerfaces hold high promise for future bioelectronics and protheses.
Optoelectronic biointerfaces have made a significant impact on modern science and technology from understanding the mechanisms of the neurotransmission to the recovery of the vision for blinds. They ...are based on the cell interfaces made of organic or inorganic materials such as silicon, graphene, oxides, quantum dots, and π‐conjugated polymers, which are dry and stiff unlike a cell/tissue environment. On the other side, wet and soft hydrogels have recently been started to attract significant attention for bioelectronics because of its high‐level tissue‐matching biomechanics and biocompatibility. However, it is challenging to obtain optimal opto‐bioelectronic devices by using hydrogels requiring device, heterojunction, and hydrogel engineering. Here, an optoelectronic biointerface integrated with a poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate), PEDOT:PSS, hydrogel that simultaneously achieves efficient, flexible, stable, biocompatible, and safe photostimulation of cells is demonstrated. Besides their interfacial tissue‐like biomechanics, ≈34 kPa, and high‐level biocompatibility, hydrogel‐integration facilitates increase in charge injection amounts sevenfolds with an improved responsivity of 156 mA W−1, stability under mechanical bending , and functional lifetime over three years. Finally, these devices enable stimulation of individual hippocampal neurons and photocontrol of beating frequency of cardiac myocytes via safe charge‐balanced capacitive currents. Therefore, hydrogel‐enabled optoelectronic biointerfaces hold great promise for next‐generation wireless neural and cardiac implants.
Neural stimulation is a fundamental tool for neurological treatments. Optoelectronic biointerfaces offer unique features with wireless and less‐invasive interaction with neurons. Their for‐the‐first‐time integration with hydrogels uniquely brings tissue‐like mechanics with boosted capacitive photocurrents for safe and efficient stimulation of neurons. This study additionally shows the great potential of poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate), PEDOT:PSS, hydrogels for optoelectronic control of beating frequency of cardiac cells.
Light-activated biointerfaces provide a non-genetic route for effective control of neural activity. InP quantum dots (QDs) have a high potential for such biomedical applications due to their uniquely ...tunable electronic properties, photostability, toxic-heavy-metal-free content, heterostructuring, and solution-processing ability. However, the effect of QD nanostructure and biointerface architecture on the photoelectrical cellular interfacing remained unexplored. Here, we unravel the control of the photoelectrical response of InP QD-based biointerfaces
nanoengineering from QD to device-level. At QD level, thin ZnS shell growth (∼0.65 nm) enhances the current level of biointerfaces over an order of magnitude with respect to only InP core QDs. At device-level, band alignment engineering allows for the bidirectional photoelectrochemical current generation, which enables light-induced temporally precise and rapidly reversible action potential generation and hyperpolarization on primary hippocampal neurons. Our findings show that nanoengineering QD-based biointerfaces hold great promise for next-generation neurostimulation devices.
Medical microrobotics is an emerging field to revolutionize clinical applications in diagnostics and therapeutics of various diseases. On the other hand, the mobile microrobotics field has important ...obstacles to pass before clinical translation. This article focuses on these challenges and provides a roadmap of medical microrobots to enable their clinical use. From the concept of a “magic bullet” to the physicochemical interactions of microrobots in complex biological environments in medical applications, there are several translational steps to consider. Clinical translation of mobile microrobots is only possible with a close collaboration between clinical experts and microrobotics researchers to address the technical challenges in microfabrication, safety, and imaging. The clinical application potential can be materialized by designing microrobots that can solve the current main challenges, such as actuation limitations, material stability, and imaging constraints. The strengths and weaknesses of the current progress in the microrobotics field are discussed and a roadmap for their clinical applications in the near future is outlined.
The clinical use of medical microrobots gets closer to reality with the rapidly growing biomedical research on them. However, the clinical translation of microrobots has several challenges and obstacles, including scalability, biocompatibility, and imaging. In this review article, a realistic roadmap for medical microrobots is conceptualized with the collaborative efforts of microrobot researchers and clinicians.
Microparticle manipulation and trapping play pivotal roles in biotechnology. To achieve effective manipulation within fluidic flow conditions and confined spaces, it is necessary to consider the ...physical properties of microparticles and the types of trapping forces applied. While acoustic waves have shown potential for manipulating microparticles, the existing setups involve complex actuation mechanisms and unstable microbubbles. Consequently, the need persists for an easily deployable acoustic actuation setup with stable microparticles. Here, we propose the use of hollow borosilicate microparticles possessing a rigid thin shell, which can be efficiently trapped and manipulated using a single-lens focused ultrasound (FUS) transducer under physiologically relevant flow conditions. These hollow microparticles offer stability and advantageous acoustic properties. They can be scaled up and mass-produced, making them suitable for systemic delivery. Our research demonstrates the successful trapping dynamics of FUS within circular tubings of varying diameters, validating the effectiveness of the method under realistic flow rates and ultrasound amplitudes. We also showcase the ability to remove hollow microparticles by steering the FUS transducer against the flow. Furthermore, we present potential biomedical applications, such as active cell tagging and navigation in bifurcated channels as well as ultrasound imaging in mouse cadaver liver tissue.
Controlled microrobotic navigation inside the body possesses significant potential for various biomedical engineering applications. Successful application requires considering imaging, control, and ...biocompatibility. Interaction with biological environments is also a crucial factor in ensuring safe application, but can also pose counterintuitive hydrodynamic barriers, limiting the use of microrobots. Surface rolling microrobots or surface microrollers is a robust microrobotic platform with significant potential for various applications; however, conventional spherical microrollers have limited locomotion ability over biological surfaces due to microtopography effects resulting from cell microtopography in the size range of 2-5 µm. Here, the impact of the microtopography effect on spherical microrollers of different sizes (5, 10, 25, and 50 µm) is investigated using computational fluid dynamics simulations and experiments. Simulations revealed that the microtopography effect becomes insignificant for increasing microroller sizes, such as 50 µm. Moreover, it is demonstrated that 50 µm microrollers exhibited smooth locomotion ability on in vitro cell layers and inside blood vessels of a chicken embryo model. These findings offer rational design principles for surface microrollers for their potential practical biomedical applications.
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