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1.
Reprod Biol ; 24(3): 100920, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38970979

RESUMO

At present, the success of non-surgical embryo recovery (NSER) and transfer (NSET) hinges upon the cervical passage of catheters, but penetration of the uterine cervix in ewes is problematic due to its anatomical structure (i.e., long and narrow cervical lumen with misaligned folds and rings). It is a major obstacle limiting the widespread application of NSER and NSET in sheep. While initial attempts to traverse the uterine cervix focused on adapting or re-designing insemination catheters, more recent studies demonstrated that cervical relaxation protocols were instrumental for transcervical penetration in the ewe. An application of such protocols more than tripled cervical penetration rates (currently at 90-95 %) in sheep of different breeds (e.g., Dorper, Lacaune, Santa Inês, crossbred, and indigenous Brazilian breeds) and ages/parity. There is now sufficient evidence to suggest that even repeatedly performed cervical passages do not adversely affect overall health and reproductive function of ewes. Despite these improvements, appropriate selection of donors and recipients remains one of the most important requirements for maintaining high success rates of NSER and NSET, respectively. Non-surgical ovine embryo recovery has gradually become a commercially viable method as even though the procedure still cannot be performed by untrained individuals, it is inexpensive, yields satisfactory results, and complies with current public expectations of animal welfare standards. This article reviews critical morphophysiological aspects of transcervical embryo flushing and transfer, and the prospect of both techniques to replace surgical methods for multiple ovulation and embryo transfer (MOET) programs in sheep. We have also discussed some potential pharmacological and technical developments in the field of non-invasive embryo recovery and deposition.

2.
Micromachines (Basel) ; 15(6)2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38930758

RESUMO

Partial-thickness corneal transplants using a deep anterior lamellar keratoplasty (DALK) approach has demonstrated better patient outcomes than a full-thickness cornea transplant. However, despite better clinical outcomes from the DALK procedure, adoption of the technique has been limited because the accurate insertion of the needle into the deep stroma remains technically challenging. In this work, we present a novel hands-free eye mountable robot for automatic needle placement in the cornea, AutoDALK, that has the potential to simplify this critical step in the DALK procedure. The system integrates dual light-weight linear piezo motors, an OCT A-scan distance sensor, and a vacuum trephine-inspired design to enable the safe, consistent, and controllable insertion of a needle into the cornea for the pneumodissection of the anterior cornea from the deep posterior cornea and Descemet's membrane. AutoDALK was designed with feedback from expert corneal surgeons and performance was evaluated by finite element analysis simulation, benchtop testing, and ex vivo experiments to demonstrate the feasibility of the system for clinical applications. The mean open-loop positional deviation was 9.39 µm, while the system repeatability and accuracy were 39.48 µm and 43.18 µm, respectively. The maximum combined thrust of the system was found to be 1.72 N, which exceeds the clinical penetration force of the cornea. In a head-to-head ex vivo comparison against an expert surgeon using a freehand approach, AutoDALK achieved more consistent needle depth, which resulted in fewer perforations of Descemet's membrane and significantly deeper pneumodissection of the stromal tissue. The results of this study indicate that robotic needle insertion has the potential to simplify the most challenging task of the DALK procedure, enable more consistent surgical outcomes for patients, and standardize partial-thickness corneal transplants as the gold standard of care if demonstrated to be more safe and more effective than penetrating keratoplasty.

3.
Angew Chem Int Ed Engl ; : e202409472, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38889093

RESUMO

With the aim of producing a photomechanical material for incorporation in soft microrobots, a one-dimensional diene coordination polymer (CP) [Cd(F-bpeb)(3-CBA)2]n (CP1, F-bpeb = 4,4'-((1E,1'E)-(2,5-difluoro-1,4-phenylene)bis(ethene-2,1-diyl))dipyri-dine, 3-HCBA = 3-chlorobenzoic acid) was synthesized and characterized. Irradiation of CP1 with ultraviolet (UV) or visible light causes [2+2] photocycloaddition reactions resulting in the introduction of crystal strain which triggers various types of crystal movements. Composite films of CP1-PVA (SC) fabricated by dispersing CP1 crystals into polyvinyl alcohol (PVA) solution allow amplification of the crystal movement so that the film strips exhibit fast and flexible curling upon photoirradiation. The composite films may be cut into long rectangular strips and folded to simulate soft microrobots which exhibit a variety of fast, flexible and continuous photomechanical movements resembling a human performing various gymnastic exercises.

4.
ACS Appl Mater Interfaces ; 16(14): 17339-17346, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38531044

RESUMO

Living organisms inspire the design of microrobots, but their functionality is unmatched. Next-generation microrobots aim to leverage the sensing and communication abilities of organisms through magnetic hybridization, attaching magnetic particles to them for external control. However, the protocols used for magnetic hybridization are morphology specific and are not generalizable. We propose an alternative approach that leverages the principles of negative magnetostatics and magnetophoresis to control nonmagnetic organisms with external magnetic fields. To do this, we disperse model organisms in dispersions of Fe3O4 nanoparticles and expose them to either uniform or gradient magnetic fields. In uniform magnetic fields, living organisms align with the field due to external torque, while gradient magnetic fields generate a negative magnetophoretic force, pushing objects away from external magnets. The magnetic fields enable controlling the position and orientation of Caenorhabditis elegans larvae and flagellated bacteria through directional interactions and magnitude. This control is diminished in live spermatozoa and adult C. elegans due to stronger internal biological activity, i.e., force/torque. Our study presents a method for spatiotemporal organization of living organisms without requiring magnetic hybridization, opening the way for the development of controllable living microbiorobots.


Assuntos
Caenorhabditis elegans , Nanopartículas , Animais , Magnetismo , Imãs , Campos Magnéticos
5.
Adv Mater ; 36(23): e2311462, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38380776

RESUMO

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.


Assuntos
Robótica , Humanos , Microtecnologia/métodos , Pesquisa Translacional Biomédica , Desenho de Equipamento
6.
Micromachines (Basel) ; 15(2)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38399003

RESUMO

The development of functional microsystems and microrobots that have characterized the last decade is the result of a synergistic and effective interaction between the progress of fabrication techniques and the increased availability of smart and responsive materials to be employed in the latter. Functional structures on the microscale have been relevant for a vast plethora of technologies that find application in different sectors including automotive, sensing devices, and consumer electronics, but are now also entering medical clinics. Working on or inside the human body requires increasing complexity and functionality on an ever-smaller scale, which is becoming possible as a result of emerging technology and smart materials over the past decades. In recent years, additive manufacturing has risen to the forefront of this evolution as the most prominent method to fabricate complex 3D structures. In this review, we discuss the rapid 3D manufacturing techniques that have emerged and how they have enabled a great leap in microrobotic applications. The arrival of smart materials with inherent functionalities has propelled microrobots to great complexity and complex applications. We focus on which materials are important for actuation and what the possibilities are for supplying the required energy. Furthermore, we provide an updated view of a new generation of microrobots in terms of both materials and fabrication technology. While two-photon lithography may be the state-of-the-art technology at the moment, in terms of resolution and design freedom, new methods such as two-step are on the horizon. In the more distant future, innovations like molecular motors could make microscale robots redundant and bring about nanofabrication.

7.
Adv Mater ; 36(1): e2300560, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37358049

RESUMO

Liquid metals, with their unique combination of electrical and mechanical properties, offer great opportunities for actuation based on surface tension modulation. Thanks to the scaling laws of surface tension, which can be electrochemically controlled at low voltages, liquid metal actuators stand out from other soft actuators for their remarkable characteristics such as high contractile strain rates and higher work densities at smaller length scales. This review summarizes the principles of liquid metal actuators and discusses their performance as well as theoretical pathways toward higher performances. The objective is to provide a comparative analysis of the ongoing development of liquid metal actuators. The design principles of the liquid metal actuators are analyzed, including low-level elemental principles (kinematics and electrochemistry), mid-level structural principles (reversibility, integrity, and scalability), and high-level functionalities. A wide range of practical use cases of liquid metal actuators from robotic locomotion and object manipulation to logic and computation is reviewed. From an energy perspective, strategies are compared for coupling the liquid metal actuators with an energy source toward fully untethered robots. The review concludes by offering a roadmap of future research directions of liquid metal actuators.

8.
Small ; 20(11): e2304773, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37936335

RESUMO

Practical applications of synthetic self-propelled nano and microparticles for microrobotics, targeted drug delivery, and manipulation at the nanoscale are rapidly expanding. However, fabrication limitations often hinder progress, resulting in relatively simple shapes and limited functionality. Here, taking advantage of 3D nanoscale printing, chiral micropropellers powered by the hydrogen peroxide reduction reaction are fabricated. Due to their chirality, the propellers exhibit multifunctional behavior controlled by an applied magnetic field: spinning in place (loitering), directed migration in the prescribed direction, capture, and transport of polymer cargo particles. Design parameters of the propellers are optimized by computation modeling based on mesoscale molecular dynamics. It is predicted by computer simulations, and confirmed experimentally, that clockwise rotating propellers attract each other and counterclockwise repel. These results shed light on how chirality and shape optimization enhance the functionality of synthetic autonomous micromachines.

9.
Adv Mater ; 36(11): e2310100, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37935054

RESUMO

Since the pioneering work of Kawata and colleagues in 1997, multi-photon 3D laser printing, also known as direct laser writing, has made significant advancements in a wide range of fields. Moreover, the development and commercialization of photocurable inks for this technique have expanded rapidly. One of the current trends is the transition from static to active printable materials, often referred to as 4D microprinting, which enables a new degree of control in the printed systems. This review focuses on four primary application areas: microrobotics, optics and photonics, microfluidics, and life sciences, highlighting recent progress and the crucial role of active materials, including liquid crystalline elastomers, hydrogels, shape memory polymers, and composites, among others. It also addresses ongoing challenges and provides insights into the future prospects in the different fields.

10.
Artigo em Inglês | MEDLINE | ID: mdl-37917969

RESUMO

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.

11.
Molecules ; 28(15)2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37570901

RESUMO

Diffusion is one of the key nature processes which plays an important role in respiration, digestion, and nutrient transport in cells. In this regard, the present article aims to review various diffusion approaches used to fabricate different functional materials based on hydrogels, unique examples of materials that control diffusion. They have found applications in fields such as drug encapsulation and delivery, nutrient delivery in agriculture, developing materials for regenerative medicine, and creating stimuli-responsive materials in soft robotics and microrobotics. In addition, mechanisms of release and drug diffusion kinetics as key tools for material design are discussed.


Assuntos
Robótica , Polímeros Responsivos a Estímulos , Hidrogéis , Sistemas de Liberação de Medicamentos , Eletrônica
12.
ACS Nano ; 17(14): 12971-12999, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37432675

RESUMO

Swarms, which stem from collective behaviors among individual elements, are commonly seen in nature. Since two decades ago, scientists have been attempting to understand the principles of natural swarms and leverage them for creating artificial swarms. To date, the underlying physics; techniques for actuation, navigation, and control; field-generation systems; and a research community are now in place. This Review reviews the fundamental principles and applications of micro/nanorobotic swarms. The generation mechanisms of the emergent collective behaviors among the micro/nanoagents identified over the past two decades are elucidated. The advantages and drawbacks of different techniques, existing control systems, major challenges, and potential prospects of micro/nanorobotic swarms are discussed.

13.
Small ; 19(47): e2303396, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37488686

RESUMO

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.


Assuntos
Engenharia Biomédica , Locomoção , Embrião de Galinha , Animais
14.
Proc Natl Acad Sci U S A ; 120(24): e2221913120, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37276400

RESUMO

At the microscale, coupled physical interactions between collectives of agents can be exploited to enable self-organization. Past systems typically consist of identical agents; however, heterogeneous agents can exhibit asymmetric pairwise interactions which can be used to generate more diverse patterns of self-organization. Here, we study the effect of size heterogeneity in microrobot collectives composed of circular, magnetic microdisks on a fluid-air interface. Each microrobot spins or oscillates about its center axis in response to an external oscillating magnetic field, in turn producing local magnetic, hydrodynamic, and capillary forces that enable diverse collective behaviors. We demonstrate through physical experiments and simulations that the heterogeneous collective can exploit the differences in microrobot size to enable programmable self-organization, density, morphology, and interaction with external passive objects. Specifically, we can control the level of self-organization by microrobot size, enable organized aggregation, dispersion, and locomotion, change the overall shape of the collective from circular to ellipse, and cage or expel objects. We characterize the fundamental self-organization behavior across a parameter space of magnetic field frequency, relative disk size, and relative populations; we replicate the behavior through a physical model and a swarming coupled oscillator model to show that the dominant effect stems from asymmetric interactions between the different-sized disks. Our work furthers insights into self-organization in heterogeneous microrobot collectives and moves us closer to the goal of applying such collectives to programmable self-assembly and active matter.

15.
Micromachines (Basel) ; 14(6)2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37374794

RESUMO

This study investigates the motion characteristics of soft alginate microrobots in complex fluidic environments utilizing wireless magnetic fields for actuation. The aim is to explore the diverse motion modes that arise due to shear forces in viscoelastic fluids by employing snowman-shaped microrobots. Polyacrylamide (PAA), a water-soluble polymer, is used to create a dynamic environment with non-Newtonian fluid properties. Microrobots are fabricated via an extrusion-based microcentrifugal droplet method, successfully demonstrating the feasibility of both wiggling and tumbling motions. Specifically, the wiggling motion primarily results from the interplay between the viscoelastic fluid environment and the microrobots' non-uniform magnetization. Furthermore, it is discovered that the viscoelasticity properties of the fluid influence the motion behavior of the microrobots, leading to non-uniform behavior in complex environments for microrobot swarms. Through velocity analysis, valuable insights into the relationship between applied magnetic fields and motion characteristics are obtained, facilitating a more realistic understanding of surface locomotion for targeted drug delivery purposes while accounting for swarm dynamics and non-uniform behavior.

16.
MethodsX ; 10: 102171, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37122368

RESUMO

Electromagnetic systems have been used extensively for the control of magnetically actuated objects, such as in microrheology and micro- robotics research. Therefore, optimizing the design of such systems is highly desirable. Some of the features that are lacking in most cur- rent designs are compactness, portability, and versatility. Portability is especially relevant for biomedical applications in which in vivo or in vitro testing may be conducted in locations away from the laboratory microscope. This document describes the design, fabrication, and imple- mentation of a compact, low-cost, versatile, and user-friendly device (the ModMag) capable of controlling multiple electromagnetic setups, includ- ing a two-dimensional 4-coil configuration, a 3-dimensional Helmholtz configuration, a 2-dimensional magnetic tweezer configuration, and a piezoelectric transducer for producing acoustic waves. All electronics for powering the systems are contained in a compact 10″x6"x3" case, which includes a 10″ touchscreen. A graphical user interface provides additional ease of use. The system can also be controlled remotely, allowing for more flexibility and the ability to interface with other software running on the remote computer such as proprietary camera software. Aside from the software and circuitry, we also describe the design of the electromagnetic coil setups and provide examples of the use of the ModMag in experiments.•Low cost and portable magnetic micro-robot manipulation device•Compatible with the 3 most common coil configurations (traditional, Helmholtz, tweezer).

17.
Proc Natl Acad Sci U S A ; 120(11): e2213481120, 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36881619

RESUMO

Endowing materials with the ability to sense, adapt, and respond to stimuli holds the key to a progress leap in autonomous systems. In spite of the growing success of macroscopic soft robotic devices, transferring these concepts to the microscale presents several challenges connected to the lack of suitable fabrication and design techniques and of internal response schemes that connect the materials' properties to the function of the active units. Here, we realize self-propelling colloidal clusters which possess a finite number of internal states, which define their motility and which are connected by reversible transitions. We produce these units via capillary assembly combining hard polystyrene colloids with two different types of thermoresponsive microgels. The clusters, actuated by spatially uniform AC electric fields, adapt their shape and dielectric properties, and consequently their propulsion, via reversible temperature-induced transitions controlled by light. The different transition temperatures for the two microgels enable three distinct dynamical states corresponding to three illumination intensity levels. The sequential reconfiguration of the microgels affects the velocity and shape of the active trajectories according to a pathway defined by tailoring the clusters' geometry during assembly. The demonstration of these simple systems indicates an exciting route toward building more complex units with broader reconfiguration schemes and multiple responses as a step forward in the pursuit of adaptive autonomous systems at the colloidal scale.

18.
Adv Mater ; 35(13): e2207791, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36502366

RESUMO

Microrobots can provide spatiotemporally well-controlled cargo delivery that can improve therapeutic efficiency compared to conventional drug delivery strategies. Robust microfabrication methods to expand the variety of materials or cargoes that can be incorporated into microrobots can greatly broaden the scope of their functions. However, current surface coating or direct blending techniques used for cargo loading result in inefficient loading and poor cargo protection during transportation, which leads to cargo waste, degradation and non-specific release. Herein, a versatile platform to fabricate fillable microrobots using microfluidic loading and dip sealing (MLDS) is presented. MLDS enables the encapsulation of different types of cargoes within hollow microrobots and protection of cargo integrity. The technique is supported by high-resolution 3D printing with an integrated microfluidic loading system, which realizes a highly precise loading process and improves cargo loading capacity. A corresponding dip sealing strategy is developed to encase and protect the loaded cargo whilst maintaining the geometric and structural integrity of the loaded microrobots. This dip sealing technique is suitable for different materials, including thermal and light-responsive materials. The MLDS platform provides new opportunities for microrobotic systems in targeted drug delivery, environmental sensing, and chemically powered micromotor applications.

19.
Materials (Basel) ; 15(22)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36431699

RESUMO

"How would you build a robot, the size of a bacteria, powered by light, that would swim towards the light source, escape from it, or could be controlled by means of different light colors, intensities or polarizations?" This was the question that Professor Diederik Wiersma asked PW on a sunny spring day in 2012, when they first met at LENS-the European Laboratory of Nonlinear Spectroscopy-in Sesto Fiorentino, just outside Florence in northern Italy. It was not just a vague question, as Prof. Wiersma, then the LENS director and leader of one of its research groups, already had an idea (and an ERC grant) about how to actually make such micro-robots, using a class of light-responsive oriented polymers, liquid crystal elastomers (LCEs), combined with the most advanced fabrication technique-two-photon 3D laser photolithography. Indeed, over the next few years, the LCE technology, successfully married with the so-called direct laser writing at LENS, resulted in a 60 micrometer long walker developed in Prof. Wiersma's group (as, surprisingly, walking at that stage proved to be easier than swimming). After completing his post-doc at LENS, PW returned to his home Faculty of Physics at the University of Warsaw, and started experimenting with LCE, both in micrometer and millimeter scales, in his newly established Photonic Nanostructure Facility. This paper is a review of how the ideas of using light-powered soft actuators in micromechanics and micro-robotics have been evolving in Warsaw over the last decade and what the outcomes have been so far.

20.
Front Robot AI ; 9: 1058324, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405071

RESUMO

[This corrects the article DOI: 10.3389/frobt.2022.791921.].

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