This paper demonstrates a manipulation of snowman-shaped soft microrobots under a uniform rotating magnetic field. Each microsnowman robot consists of two biocompatible alginate microspheres with embedded magnetic nanoparticles. The soft microsnowmen were fabricated using a microfluidic device by following a centrifuge-based microfluidic droplet method. Under a uniform rotating magnetic field, the microsnowmen were rolled on the substrate surface, and the velocity response for increasing magnetic field frequencies was analyzed. Then, a microsnowman was rolled to follow different paths, which demonstrated directional controllability of the microrobot. Moreover, swarms of microsnowmen and single alginate microrobots were manipulated under the rotating magnetic field, and their velocity responses were analyzed for comparison.
more »
« less
Fabrication and magnetic control of alginate-based rolling microrobots
Advances in microrobotics for biological applications are often limited due to their complex manufacturing processes, which often utilize cytotoxic materials, as well as limitations in the ability to manipulate these small devices wirelessly. In an effort to overcome these challenges, we investigated a facile method for generating biocompatible hydrogel based robots that are capable of being manipulated using an externally generated magnetic field. Here, we experimentally demonstrate the fabrication and autonomous control of loaded-alginate microspheres, which we term artificial cells. In order to generate these microparticles, we employed a centrifuge-based method in which microspheres were rapidly ejected from a nozzle tip. Specifically, we used two mixtures of sodium alginate; one containing iron oxide nanoparticles and the other containing mammalian cells. This mixture was loaded into a needle that was fixed on top of a microtube containing calcium chloride, and then briefly centrifuged to generate hundreds of Janus microspheres. The fabricated microparticles were then magnetically actuated with a rotating magnetic field, generated using electromagnetic coils, prompting the particles to roll across a glass substrate. Also, using vision-based feedback control, a single artificial cell was manipulated to autonomously move in a programmed pattern.
more »
« less
- Award ID(s):
- 1712096
- PAR ID:
- 10597286
- Publisher / Repository:
- American Institute of Physics
- Date Published:
- Journal Name:
- AIP Advances
- Volume:
- 6
- Issue:
- 12
- ISSN:
- 2158-3226
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Invasive candidiasis (IC) remains as a major cause of morbidity and mortality in critically ill patients. Amphotericin B (AmB) is one of the most effective antifungal agents commonly used to treat this infection. However, it induces severe side effects such as nephrotoxicity, cardiac alterations, nausea, fever, and liver damage. The utilization of drug delivery systems has been explored to overcome these limitations. Several AmB lipid formulations have been developed and are currently available in the market. Although they have the ability to reduce the main side effects of free AmB, their high cost, necessity of repeated intravenous injections for successful treatment, and incidence of pulmonary toxicity have limited their use. In the last decades, alginate has gained significant interest in drug delivery applications as a cost-effective strategy to improve the safety and therapeutic effect of toxic drugs. In this work, the clinically relevant drug AmB was encapsulated into alginate microparticles using the emulsification/external gelation method. We hypothesize that this synthesis strategy may positively impact the antifungal efficacy of AmB-loaded MCPs toward Candida albicans cells while reducing the toxicity in human lung cells. To prove this hypothesis, the ability of the microplatform to disrupt the cellular membrane potential was tested and its antifungal effectiveness toward Candida albicans cells was evaluated using the cell counting and plate count methods. Moreover, the toxicity of the microplatform in human lung cells was evaluated using CellTiter 96® AQueous cell viability assay and qualitative diffusion analysis of acridine orange. Our results demonstrated that the platform developed in this work was able to induce antifungal toxicity against Candida albicans yeast cells at the same level of free AmB with minimal toxicity to lung cells, which is one of the main side effects induced by commercial drug delivery systems containing AmB. Overall, our data provides convincing evidence about the effectiveness of the alginate-based microplatform toward Candida albicans cells. In addition, this vehicle may not require several infusions for a successful treatment while reducing the pulmonary toxic effect induced by commercial lipid formulations.more » « less
-
This paper presents experimental results to verify a novel concept of magnetic manipulation in which arrays of permanent magnets and electromechanical actuators generate and effectively control magnetic fields, through which, magnetic objects can be manipulated from a distance without any direct contact. This concept is realized by an experimental setup that consists of six diametrically magnetized permanent magnets actuated by rotary servomotors to control their directions, by which, the aggregate magnetic field is controlled in a planar circular workspace. To leverage this magnetic field for control of magnetic objects inside the workspace, a feedback loop must be established to command the servomotors based on the positions of these objects measured in real time. A suitable control law is developed for this feedback loop, and is verified by experiments, which demonstrate successful results. The experimental results are compared with those generated by computer simulations under similar conditions.more » « less
-
Abstract Chemically coated micro/nanoparticles are often used in medicine to enhance drug delivery and increase drug up-take into specific areas of the body. Using a recently discovered spontaneous symmetry breaking propulsion mechanism, we demonstrate that chemically coated microparticles can swim through mucus solution under precise navigation and that certain functionalizations can dynamically change propulsion behavior. For this investigation biotin, Bitotin-PEG3-amine, and biotin chitosan were chemically functionalized onto the surfaces of magnetic microparticles using an avidin–biotin complex. These chemicals were chosen because they are used prolifically in drug delivery applications, with PEG and chitosan having well known mucoadhesive effects. Coated microparticles were then suspended in mucus synthesized from porcine stomach mucins and propelled using rotating magnetic fields. The relationship between different chemical coatings, microparticle velocity, and controllability were thoroughly explored and discussed. Results indicate that the biotinylated surface coatings altered the propulsion behavior of microparticles, with performance differences interlinked to both magnetic field properties and localized mucus properties. Precisely controlled drug carrying microparticles are envisioned to help supplant traditional drug delivery methods and enhance existing medical techniques utilizing micro/nanoparticles.more » « less
-
For drug discovery, new in vitro cancer models are needed to obtain more translatable study outcomes in a low-cost and high-throughput manner. For this purpose, 3D cancer spheroids have been established as more effective than 2D models. Current commercial techniques, however, rely heavily on self-aggregation of dissociated cells and cannot replicate key features of the native tumor microenvironment, particularly due to a lack of control over extracellular matrix components and heterogeneity in size and aggregate-forming tendencies. Also, current spheroidal techniques are typically limited to one spheroid per well, therefore providing a narrow range of cell numbers per well, disadvantageous for assay development in drug screening. Here, we overcome these challenges by coupling tissue engineering toolsets with microfluidic technologies to create engineered cancer microspheres and sorting desired numbers of microspheres into assay-ready well-plate format. To form the engineered cancer microspheres, MCF7 (non-metastatic) and MDA-MB-231 (metastatic) breast cancer cells were encapsulated within poly(ethylene glycol)-fibrinogen hydrogels using our previously developed microfluidic platform. Highly uniform cancer microspheres (intra and inter-batch coefficient of variation ≤ 5%) with high cell densities (over 20 × 106 cells/ml) were produced rapidly, which is critical for use in drug testing. The microspheres supported the 3D culture of both breast cancer cell lines over at least 14 days in culture. Encapsulated cells displayed cell type-specific differences in morphology, proliferation, metabolic activity, ultrastructure, and overall microsphere size distribution and bulk stiffness. To prepare assay-ready pre-plated microspheres, a COPAS FP flow cytometer was used for its ability to analyze and sort large sample particles such as tumor spheroids and hydrogel cancer microspheres generated in this study. When using a 96-well plate, the sorting rate varied from 2.5 - 6 microspheres per second, depending on the sample concentration. When sorting a desired number of microspheres per well, the accuracy was greater than 95% as verified visually by microscopy. Viability of sorted microspheres was verified 24 hours post-sort. Shipping conditions were established that maintained cell viability for remote use in drug testing. Methods for compound addition by pinning and imaging were tested and optimized. Using these approaches, the microsphere system was shown to be compatible with an automated liquid handling system for administration of drug compounds; MDA-MB-231 microspheres were distributed in 384 well plates and treated with chemotherapeutic drugs. Expected responses were quantitated using CellTiter-Glo® 3D and detected using automated imaging. Overall, our results demonstrate initial applicability for the tissue-engineered cancer microspheres for drug screening.more » « less
An official website of the United States government
