No abstract

Biocompatible functional materials play a significant role in drug delivery, tissue engineering and single cell analysis. We utilized 3D printing to produce high aspect ratio polymer resist microneedles on a silicon substrate and functionalized them by iron coating. Two-photon polymerization lithography has been used for printing cylindrical, pyramidal, and conical needles from a drop cast IP-DIP resist. Experiments with cells were conducted with cylindrical microneedles with 630  15 nm in diameter with an aspect ratio of 1:10 and pitch of 12 m. The needles have been arranged in square shaped arrays with various dimensions. The iron coating of the needles was 120  15 nm thick and has isotropic magnetic behavior. The chemical composition and oxidation state were determined using energy electron loss spectroscopy, revealing a mixture of iron and Fe3O4 clusters. A biocompatibility assessment was performed through fluorescence microscopy using calcein/EthD-1 live/dead assay. The results show a very high biocompatibility of the iron coated needle arrays. This study provides a strategy to obtain electromagnetically functional microneedles that benefit from the flexibility in terms of geometry and shape of 3D printing. Potential applications are in areas like tissue engineering, single cell analysis or drug delivery.

Highly efficient magnetic release from nanocomposite microparticles is shown, which are made of Poly (N-isopropylacrylamide) hydrogel with embedded iron nanowires. A simple microfluidic technique was adopted to fabricate the microparticles with a high control of the nanowire concentration and in a relatively short time compared to chemical synthesis methods. The thermoresponsive microparticles were used for the remotely triggered release of Rhodamine (B). With a magnetic field of only 1 mT and 20 kHz a drug release of 6.5% and 70% was achieved in the continuous and pulsatile modes, respectively. Those release values are similar to the ones commonly obtained using superparamagnetic beads but accomplished with a magnetic field of five orders of magnitude lower power. The high efficiency is a result of the high remanent magnetization of the nanowires, which produce a large torque when exposed to a magnetic field. This causes the nanowires to vibrate, resulting in friction losses and heating. For comparison, microparticles with superparamagnetic beads were also fabricated and tested; while those worked at 73 mT and 600 kHz, no release was observed at the low field conditions. Cytotoxicity assays showed similar and high cell viability for microparticles with nanowires and beads.

Methods that provide controlled influx of molecules into cells are of critical importance for uncovering cellular mechanisms, drug development and synthetic biology. However, reliable intracellular delivery without adversely affecting the cells is a major challenge. We developed a platform for on-demand intracellular delivery applications, with which cell membrane penetration is achieved by inductive heating of micro needles. The micro needles of around 1 μm in diameter and 5 μm in length are made of gold using a silicon-based micro fabrication process that provides flexibility with respect to the needles’ dimensions, pitch, shell thickness and the covered area. Experiments with HCT 116 colon cancer cells showed a high biocompatibility of the gold needle platform. Transmission electron microscopy of the cell-needle interface revealed folding of the cell membrane around the needle without penetration, preventing any delivery, which was confirmed using the EthD-1 fluorescent dye. The application of an alternating magnetic field, however, resulted in the delivery of EthD-1 by localized heating of the micro needles. Fluorescence quantification showed that intracellular delivery, with as high as 75% efficiency, is achieved for specific treatment times between 1 and 5 minutes. Overexposure of the cells to the heated micro needles, i.e. longer magnetic field application, leads to an increase in cell death, which can be exploited for cleaning the platform. This method allows to perform intracellular deliver by remotely activating the micro needles via a magnetic field, and it is controlled by the application time, making it a versatile and easy to use method. The wireless actuation could also be an attractive feature for in-vivo delivery and implantable devices.

Responsive microgel poly(N-isopropylacrylamide) or PNIPAM is a gel that can swell or shrink in response to external stimuli (temperature, pH, etc.). In this work, a nanocomposite gel is developed consisting of PNIPAM and magnetic iron oxide nanobeads for controlled release of liquids (like drugs) upon exposure to an alternating magnetic field. Microparticles of the nanocomposite are fabricated efficiently with a monodisperse size distribution and a diameter ranging from 20 to 500 µm at a rate of up to 1 kHz using a simple and inexpensive microfluidic system. The nanocomposite is heated through magnetic losses, which is exploited for a remotely stimulated liquid release. The efficiency of the microparticles for controlled drug release applications is tested with a solution of Rhodamine B as a liquid drug model. In continuous and pulsatile mode, a release of 7% and 80% was achieved, respectively. Compared to external thermal actuation that heats the entire surrounding or embedded heaters that need complex fabrication steps, the magnetic actuation provides localized heating and is easy to implement with our microfluidic fabrication method.