Haptic-Based Manipulation Scheme of Magnetic Nanoparticles in a Multi-Branch Blood Vessel for Targeted Drug Delivery.
ABSTRACT: Magnetic drug targeting is a promising technique that can deliver drugs to the diseased region, while keeping the drug away from healthy parts of body. Introducing a human in the control loop of a targeted drug delivery system and using inherent bilateralism of a haptic device at the same time can considerably improve the performance of targeted drug delivery systems. In this paper, we suggest a novel intelligent haptic guidance scheme for steering a number of magnetic nanoparticles (MNPs) using forbidden region virtual fixtures and a haptic rendering scheme with multi particles. Forbidden region virtual fixtures are a general class of guidance modes implemented in software, which help a human-machine collaborative system accomplish a specific task by constraining a movement into limited regions. To examine the effectiveness of our proposed scheme, we implemented a magnetic guided drug delivery system in a virtual environment using a physics-based model of targeted drug delivery including a multi-branch blood vessel and realistic blood dynamics. We performed user studies with different guidance modes: unguided, semi virtual fixture and full virtual fixture modes. We found out that the efficiency of targeting was significantly improved using the forbidden region virtual fixture and the proposed haptic rendering of MNPs. We can expect that using intelligent haptic feedback in real targeted drug delivery systems can improve the targeting efficiency of MNPs in multi-branch vessels.
Project description:Magnetic nanoparticles (MNPs) are effective drug carriers. By using electromagnetic actuated systems, MNPs can be controlled noninvasively in a vascular network for targeted drug delivery (TDD). Although drugs can reach their target location through capturing schemes of MNPs by permanent magnets, drugs delivered to non-target regions can affect healthy tissues and cause undesirable side effects. Real-time monitoring of MNPs can improve the targeting efficiency of TDD systems. In this paper, a two-dimensional (2D) real-time monitoring scheme has been developed for an MNP guidance system. Resovist particles 45 to 65 nm in diameter (5 nm core) can be monitored in real-time (update rate = 2 Hz) in 2D. The proposed 2D monitoring system allows dynamic tracking of MNPs during TDD and renders magnetic particle imaging-based navigation more feasible.
Project description:Lighting technologies for plant growth are improving rapidly, providing numerous options for supplemental lighting in greenhouses. Here we report the photosynthetic (400-700 nm) photon efficiency and photon distribution pattern of two double-ended HPS fixtures, five mogul-base HPS fixtures, ten LED fixtures, three ceramic metal halide fixtures, and two fluorescent fixtures. The two most efficient LED and the two most efficient double-ended HPS fixtures had nearly identical efficiencies at 1.66 to 1.70 micromoles per joule. These four fixtures represent a dramatic improvement over the 1.02 micromoles per joule efficiency of the mogul-base HPS fixtures that are in common use. The best ceramic metal halide and fluorescent fixtures had efficiencies of 1.46 and 0.95 micromoles per joule, respectively. We also calculated the initial capital cost of fixtures per photon delivered and determined that LED fixtures cost five to ten times more than HPS fixtures. The five-year electric plus fixture cost per mole of photons is thus 2.3 times higher for LED fixtures, due to high capital costs. Compared to electric costs, our analysis indicates that the long-term maintenance costs are small for both technologies. If widely spaced benches are a necessary part of a production system, the unique ability of LED fixtures to efficiently focus photons on specific areas can be used to improve the photon capture by plant canopies. Our analysis demonstrates, however, that the cost per photon delivered is higher in these systems, regardless of fixture category. The lowest lighting system costs are realized when an efficient fixture is coupled with effective canopy photon capture.
Project description:The blood-brain barrier (BBB) hinders drug delivery to the brain. Despite various efforts to develop preprogramed actuation schemes for magnetic drug delivery, the unmodeled aggregation phenomenon limits drug delivery performance. This paper proposes a novel scheme with an aggregation model for a feed-forward magnetic actuation design. A simulation platform for aggregated particle delivery is developed and an actuation scheme is proposed to deliver aggregated magnetic nanoparticles (MNPs) using a discontinuous asymmetrical magnetic actuation. The experimental results with a Y-shaped channel indicated the success of the proposed scheme in steering and disaggregation. The delivery performance of the developed scheme was examined using a realistic, three-dimensional (3D) vessel simulation. Furthermore, the proposed scheme enhanced the transport and uptake of MNPs across the BBB in mice. The scheme presented here facilitates the passage of particles across the BBB to the brain using an electromagnetic actuation scheme.
Project description:Humans have the ability to use a diverse range of handheld tools. Owing to its versatility, a virtual environment with haptic feedback of the force is ideally suited to investigating motor learning during tool use. However, few simulators exist to recreate the dynamic interactions during real tool use, and no study has compared the correlates of motor learning between a real and virtual tooling task. To this end, we compared two groups of participants who either learned to insert a real or virtual tool into a fixture. The trial duration, the movement speed, the force impulse after insertion and the endpoint stiffness magnitude decreased as a function of trials, but they changed at comparable rates in both environments. A ballistic insertion strategy observed in both environments suggests some interdependence when controlling motion and controlling interaction, contradicting a prominent theory of these two control modalities being independent of one another. Our results suggest that the brain learns real and virtual insertion in a comparable manner, thereby supporting the use of a virtual tooling task with haptic feedback to investigate motor learning during tool use.
Project description:BACKGROUND: Arthroscopic surgical training is inherently difficult due to limited visibility, reduced motion freedom and non-intuitive hand-eye coordination. Traditional training methods as well as virtual reality approach lack the direct guidance of an experienced physician. METHODS: This paper presents an experience-based arthroscopic training simulator that integrates motion tracking with a haptic device to record and reproduce the complex trajectory of an arthroscopic inspection procedure. Optimal arthroscopic operations depend on much practice because the knee joint space is narrow and the anatomic structures are complex. The trajectory of the arthroscope from the experienced surgeon can be captured during the clinical treatment. Then a haptic device is used to guide the trainees in the virtual environment to follow the trajectory. RESULTS: In this paper, an experiment for the eight subjects' performance of arthroscopic inspection on the same simulator was done with and without the force guidance. The experiment reveals that most subjects' performances are better after they repeated the same inspection five times. Furthermore, most subjects' performances with the force guidance are better than those without the force guidance. In the experiment, the average error with the force guidance is 33.01% lower than that without the force guidance. The operation time with the force guidance is 14.95% less than that without the force guidance. CONCLUSIONS: We develop a novel virtual knee arthroscopic training system with virtual and haptic guidance. Compared to traditional VR training system that only has a single play-script based on a virtual model, the proposed system can track and reproduce real-life arthroscopic procedures and create a useful training database. From our experiment, the force guidance can efficiently shorten the learning curve of novice trainees. Through such system, novice trainees can efficiently develop required surgical skills by the virtual and haptic guidance from an experienced surgeon.
Project description:In this paper, a novel haptic feedback scheme, used for accurately positioning a 1DOF virtual wrist prosthesis through sensory substitution, is presented. The scheme employs a three-node tactor array and discretely and selectively modulates the stimulation frequency of each tactor to relay 11 discrete haptic stimuli to the user. Able-bodied participants were able to move the virtual wrist prosthesis via a surface electromyography based controller. The participants evaluated the feedback scheme without visual or audio feedback and relied solely on the haptic feedback alone to correctly position the hand. The scheme was evaluated through both normal (perpendicular) and shear (lateral) stimulations applied on the forearm. Normal stimulations were applied through a prototype device previously developed by the authors while shear stimulations were generated using an ubiquitous coin motor vibrotactor. Trials with no feedback served as a baseline to compare results within the study and to the literature. The results indicated that using normal and shear stimulations resulted in accurately positioning the virtual wrist, but were not significantly different. Using haptic feedback was substantially better than no feedback. The results found in this study are significant since the feedback scheme allows for using relatively few tactors to relay rich haptic information to the user and can be learned easily despite a relatively short amount of training. Additionally, the results are important for the haptic community since they contradict the common conception in the literature that normal stimulation is inferior to shear. From an ergonomic perspective normal stimulation has the potential to benefit upper limb amputees since it can operate at lower frequencies than shear-based vibrotactors while also generating less noise. Through further tuning of the novel haptic feedback scheme and normal stimulation device, a compact and comfortable sensory substitution device for upper limb amputees might be created.
Project description:The interaction of macrophages with micro and nanoparticles (MNPs) is important because these cells clear particles from the circulation, and because they are potential therapeutic targets in inflammatory conditions, atherosclerosis and cancer. Therefore, an understanding of the features of MNPs that influence their interaction with macrophages may allow optimization of their properties for enhanced drug delivery. In this study, we show that particle shape impacts phagocytosis by macrophages, and more importantly, that particle shape and size separately impact attachment and internalization. The study provides a methodology for further exploring how particle shape can be controlled to achieve desired attachment and internalization. The results of the study also give mechanistic guidance on how particle shape can be manipulated to design drug carriers to evade macrophages, or alternatively to target macrophages.
Project description:With the decrease in the number of cerebral aneurysms treated surgically and the increase of complexity of those treated surgically, there is a need for simulation-based tools to teach future neurosurgeons the operative techniques of aneurysm clipping.To develop and evaluate the usefulness of a new haptic-based virtual reality simulator in the training of neurosurgical residents.A real-time sensory haptic feedback virtual reality aneurysm clipping simulator was developed using the ImmersiveTouch platform. A prototype middle cerebral artery aneurysm simulation was created from a computed tomographic angiogram. Aneurysm and vessel volume deformation and haptic feedback are provided in a 3-dimensional immersive virtual reality environment. Intraoperative aneurysm rupture was also simulated. Seventeen neurosurgery residents from 3 residency programs tested the simulator and provided feedback on its usefulness and resemblance to real aneurysm clipping surgery.Residents thought that the simulation would be useful in preparing for real-life surgery. About two-thirds of the residents thought that the 3-dimensional immersive anatomic details provided a close resemblance to real operative anatomy and accurate guidance for deciding surgical approaches. They thought the simulation was useful for preoperative surgical rehearsal and neurosurgical training. A third of the residents thought that the technology in its current form provided realistic haptic feedback for aneurysm surgery.Neurosurgical residents thought that the novel immersive VR simulator is helpful in their training, especially because they do not get a chance to perform aneurysm clippings until late in their residency programs.
Project description:Visuo-haptic biases are observed when bringing your unseen hand to a visual target. The biases are different between, but consistent within participants. We investigated the usefulness of adjusting haptic guidance to these user-specific biases in aligning haptic and visual perception. By adjusting haptic guidance according to the biases, we aimed to reduce the conflict between the modalities. We first measured the biases using an adaptive procedure. Next, we measured performance in a pointing task using three conditions: 1) visual images that were adjusted to user-specific biases, without haptic guidance, 2) veridical visual images combined with haptic guidance, and 3) shifted visual images combined with haptic guidance. Adding haptic guidance increased precision. Combining haptic guidance with user-specific visual information yielded the highest accuracy and the lowest level of conflict with the guidance at the end point. These results show the potential of correcting for user-specific perceptual biases when designing haptic guidance.
Project description:INTRODUCTION: Expansion of efficacious theranostic systems is of pivotal significance for medicine and human healthcare. Magnetic nanoparticles (MNPs) are known as drug delivery system and magnetic resonance imaging (MRI) contrast agent. MNPs as drug carriers have attracted significant attention because of the delivery of drugs loaded onto MNPs to solid tumors, maintaining them in the target site by an external electromagnetic field, and subsequently releasing drugs in a controlled manner. On the other hand, it is believed that MNPs possess high potential as MRI contrast agents. The aim of this work was to payload curcumin into dextran coated MNPs and investigate their potential as theranostic systems for controlled drug delivery and MRI imaging. METHODS: MNPs were synthesized as a core and coated with dextran as polymeric shell to provide steric stabilization. Curcumin as anticancer drug was selected to be loaded into NPs. To characterize the synthesized NPs, various techniques (e.g., DLS, FESEM, FT-IR, XRD, and VSM) were utilized. In vitro drug release of curcumin was evaluated at 37˚C at the pH value of 5.4 and 7.4.The feasibility of employment of dextran coated MNPs as MRI contrast agents were also studied. RESULTS: Formulations prepared from dextran coated MNPs showed high loading (13%) and encapsulation efficiency (95%). In vitro release study performed in the phosphate-buffered saline (PBS, pH= 7.4, 5.4) revealed that the dextran coated MNPs possess sustained release behavior at least for 4 days with the high extent of drug release in acidic media. Vibrating sample magnetometer (VSM) analysis proved the superparamagnetic properties of the dextran coated MNPs with relatively high-magnetization value indicating that they were sufficiently sensitive to external magnetic fields as magnetic drug carriers. Furthermore, dextran coated MNPs exhibited high potential as T2 contrast agents for MRI. CONCLUSION: Based on our findings, we propose the dextran coated MNPs as promising nanosystem for the delivery of various drugs such as curcumin and MRI contrast agent.