Soft micro‐ and nanostructures have been extensively developed for biomedical applications. The main focus has been on multifunctional composite materials that combine the advantages of hydrogels and colloidal particles. Magnetic microgels and nanogels can be realized by hybridizing stimuli‐sensitive gels and magnetic nanoparticles. They are of particular interest since they can be controlled in a wide range of biological environments by using magnetic fields. In this review, we elucidate physical principles underlying the design of magnetic microgels and nanogels for biomedical applications. Particularly, this article provides a comprehensive and conceptual overview on the correlative structural design and physical functionality of the magnetic gel systems under the concept of colloidal biodevices. To this end, we begin with an overview of physicochemical mechanisms related to stimuli‐responsive hydrogels and transport phenomena and summarize the magnetic properties of inorganic nanoparticles. On the basis of the engineering principles, we categorize and summarize recent advances in magnetic hybrid microgels and nanogels, with emphasis on the biomedical applications of these materials. Potential applications of these hybrid microgels and nanogels in anticancer treatment, protein therapeutics, gene therapy, bioseparation, biocatalysis, and regenerative medicine are highlighted. Finally, current challenges and future opportunities in the design of smart colloidal biodevices are discussed.
Magnetic dot arrays with perpendicular magnetic anisotropy were fabricated by patterning Co(80)Pt(20)-alloy continuous films by means of laser interference lithography. As commonly seen in large dot arrays, there is a large difference in the switching field between dots. Here we investigate the origin of this large switching field distribution, by using the anomalous Hall effect (AHE). The high sensitivity of the AHE permits us to measure the magnetic reversal of individual dots in an array of 80 dots with a diameter of 180 nm. By taking 1000 hysteresis loops we reveal the thermally induced switching field distribution SFD(T) of individual dots inside the array. The SFD(T) of the first and last switching dots were fitted to an Arrhenius model, and a clear difference in switching volume and magnetic anisotropy was observed between dots switching at low and high fields.
Due to the low frequency of circulating tumor cells (CTC), the standard CellSearch method of enumeration and isolation using a single tube of blood is insufficient to measure treatment effects consistently, or to steer personalized therapy. Using diagnostic leukapheresis this sample size can be increased; however, this also calls for a suitable new method to process larger sample inputs. In order to achieve this, we have optimized the immunomagnetic enrichment process using a flow-through magnetophoretic system. An overview of the major forces involved in magnetophoretic separation is provided and the model used for optimizing the magnetic configuration in flow through immunomagnetic enrichment is presented. The optimal Halbach array element size was calculated and both optimal and non-optimal arrays were built and tested using anti-EpCAM ferrofluid in combination with cell lines of varying EpCAM antigen expression. Experimentally measured distributions of the magnetic moment of the cell lines used for comparison were combined with predicted recoveries and fit to the experimental data. Resulting predictions agree with measured data within measurement uncertainty. The presented method can be used not only to optimize magnetophoretic separation using a variety of flow configurations but could also be adapted to optimize other (static) magnetic separation techniques.
Individual biohybrid microrobots have the potential to perform biomedical in vivo tasks such as remote-controlled drug and cell delivery and minimally invasive surgery. This work demonstrates the formation of biohybrid sperm-templated clusters under the influence of an external magnetic field and essential functionalities for wireless actuation and drug delivery. Ferromagnetic nanoparticles are electrostatically assembled around dead sperm cells, and the resulting nanoparticle-coated cells are magnetically assembled into three-dimensional biohybrid clusters. The aim of this clustering is threefold: First, to enable rolling locomotion on a nearby solid boundary using a rotating magnetic field; second, to allow for noninvasive localization; third, to load the cells inside the cluster with drugs for targeted therapy. A magneto-hydrodynamic model captures the rotational response of the clusters in a viscous fluid, and predicts an upper bound for their step-out frequency, which is independent of their volume or aspect ratio. Below the step-out frequency, the rolling velocity of the clusters increases nonlinearly with their perimeter and actuation frequency. During rolling locomotion, the clusters are localized using ultrasound images at a relatively large distance, which makes these biohybrid clusters promising for deep-tissue applications. Finally, we show that the estimated drug load scales with the number of cells in the cluster and can be retained for more than 10 h. The aggregation of microrobots enables them to collectively roll in a predictable way in response to an external rotating magnetic field, and enhances ultrasound detectability and drug loading capacity compared to the individual microrobots. The favorable features of biohybrid microrobot clusters place emphasis on the importance of the investigation and development of collective microrobots and their potential for in vivo applications.
1 June 2010 in Journal of Micromechanics and Microengineering