We report the development of a magnetically controlled MEMS device capable of on-demand release of defined quantities of an antiproliferative drug, docetaxel (DTX). Controlled release of DTX with a dosage suitable for the treatment of diabetic retinopathy has been achieved for 35 days. The device consists of a drug-loaded microreservoir (Ø6 mm ×∼550 μm), sealed by an elastic magnetic PDMS (polydimethylsiloxane) membrane (Ø6 mm × 40 μm) with a laser-drilled aperture (∼100 × 100 μm(2)). By applying a magnetic field, the magnetic PDMS membrane deforms, causing the discharge of the drug solution from the device. Controlled DTX release at a rate of 171 ± 16.7 ng per actuation interval has been achieved for 35 days using a 255 mT magnetic field. The background leakage of drug solution through the aperture was negligible at 0.053 ± 0.014 ng min(-1). The biological activity of the released drug was investigated using a cytotoxicity assay (cell apoptosis) for two cell lines, HUVEC (human umbilical vein endothelial cells) and PC3 (prostate cancer) cells. Reproducible release rates have been achieved and DTX within the PDMS MEMS reservoir maintains full pharmacological efficacy for more than two months. This device is a proof-of-concept development for targeted delivery of hydrophobic drugs such as DTX and other taxane-based agents that require accurate delivery in nanomolar concentrations.
We report the development of a magnetically controlled drug delivery device for on-demand drug release to treat chronic diseases. The devices consist of drug-loaded micro-reservoirs (6 mm in diameter and ∼550 μm in depth), sealed by magnetic PDMS (polydimethylsiloxane) membranes (Ø 6 mm × 40 μm) with laser-drilled apertures and actuated by an external magnetic field. We present a detailed analysis of the magnetic actuation forces and provide an estimate of the resulting membrane deflections. The reservoirs are fabricated by PDMS molding and loaded with drugs using solvent evaporation methods. Post-processing procedures using bovine serum albumin (BSA) adsorption on magnetic PDMS surfaces are carried out to modify the surface wettability and to allow water filling and dissolution of the drugs in the reservoirs. Detailed surface modification processes are described and characterized. The device demonstrates on-demand delivery of methylene blue (MB) as a model drug. Intermittent magnetic actuations of the device in a ∼200 mT magnetic field show 10-fold increase in MB release compared to background release when the device is not actuated.
We report a new magnetic polymer membrane for MEMS application. The polymeric magnetic composite has coated iron oxide nanoparticles incorporated in a polydimethylsiloxane (PDMS) matrix. Existing magnetic polymeric materials have particle agglomeration problems, which result in rough surfaces and uneven mechanical and optical properties. We show that the use of iron oxide nanoparticles (10 nm in diameter) with fatty acid and hydrophobic coatings inhibits aggregation of particles in the PDMS polymer matrix. Agglomerated particle sizes in thin-film PDMS composites incorporated with uncoated and coated particles are 51 ± 24 μm and 1.6 ± 0.25 μm, respectively. The PDMS composites exhibit saturation magnetization of 22.8 to 23.94 emu g −1 . Stress-strain curves of the composites are characterized by tensile tests. Free-standing magnetic PDMS membranes are fabricated in different sizes from 4 mm to 7 mm in diameter and with the thickness of 35.5 ± 1.5 μm. The membrane of 7 mm diameter achieves deflection of 625 μm in a 0.417 T magnetic field. The magnetic PDMS membranes may be used in micro-pumps and lab-on-a-chip applications.
This paper presents a new scheme for fault detection and diagnosis (FDD) in spacecraft attitude determination (AD) sensors. An integrated attitude determination system, which includes measurements of rate and angular position using rate gyros and vector sensors, is developed. Measurement data from all sensors are fused by a linearized Kalman filter, which is designed based on the system kinematics, to provide attitude estimation and the values of the gyro bias. Using this information the erroneous sensor measurements are corrected, and unbounded sensor measurement errors are avoided. The resulting bias-free data are used in the FDD scheme. The FDD algorithm uses model-based state estimation, combining the information from the rotational dynamics and kinematics of a spacecraft with the sensor measurements to predict the future sensor outputs. Fault isolation is performed through extended Kalman filters (EKFs). The innovation sequences of EKFs are monitored by several statistical tests to detect the presence of a failure and to localize the failures in all AD sensors. The isolation procedure is developed in two phases. In the first phase, two EKFs are designed, which use subsets of measurements to provide state estimates and form residuals, which are used to verify the source of the fault. In the second phase of isolation, testing of multiple hypotheses is performed. The generalized likelihood ratio test is utilized to identify the faulty components. In the scheme developed in this paper a relatively small number of hypotheses is used, which results in faster isolation and highly distinguishable fault signatures. An important feature of the developed FDD scheme is that it can provide attitude estimations even if only one type of sensors is functioning properly.
A cylindrical magnetically-actuated MEMS drug delivery device, implanted through a needle for localized prostate cancer treatment is proposed.
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