Charilaos Mousoulis

Polymeric microdevices for transdermal and subcutaneous drug delivery

Low cost manufacturing of polymeric microdevices for transdermal and subcutaneous drug delivery is slated to have a major impact on next generation devices for administration of biopharmaceuticals and other emerging new formulations. These devices range in complexity from simple microneedle arrays to more complicated systems incorporating micropumps, micro-reservoirs, on-board sensors, and electronic intelligence. In this paper, we review devices currently in the market and those in the earlier stages of research and development. We also present two examples of the research in our laboratory towards using phase change liquids in polymeric structures to create disposable micropumps and the development of an elastomeric reservoir for MEMS-based transdermal drug delivery systems.

A Skin-Contact-Actuated Micropump for Transdermal Drug Delivery

In this paper, a skin-contact-actuated dispenser/micropump for transdermal drug delivery applications is presented. The micropump consists of stacked polydimethylsiloxane layers mounted on a silicon substrate and operates based on the evaporation and condensation of a low-boiling-point liquid. Therefore, there is no need for a heater and a power source, since only the thermal energy provided by skin contact is required for the actuation. A prototype device with overall dimensions of 14 mm × 14 mm × 8 mm is fabricated and characterized. For a perfluoro compound working fluid (3M FC-3284), a flow rate of 28.8 μ L/min and a maximum back pressure of 28.9 kPa is measured.

Single cell spectroscopy: noninvasive measures of small-scale structure and function.

The advancement of spectroscopy methods attained through increases in sensitivity, and often with the coupling of complementary techniques, has enabled real-time structure and function measurements of single cells. The purpose of this review is to illustrate, in light of advances, the strengths and the weaknesses of these methods. Included also is an assessment of the impact of the experimental setup and conditions of each method on cellular function and integrity. A particular emphasis is placed on noninvasive and nondestructive techniques for achieving single cell detection, including nuclear magnetic resonance, in addition to physical, optical, and vibrational methods.

Atomic force microscopy-coupled microcoils for cellular-scale nuclear magnetic resonance spectroscopy

We present the coupling of atomic force microscopy (AFM) and nuclear magnetic resonance (NMR) technologies to enable topographical, mechanical, and chemical profiling of biological samples. Here, we fabricate and perform proof-of-concept testing of radiofrequency planar microcoils on commercial AFM cantilevers. The sensitive region of the coil was estimated to cover an approximate volume of 19.4 × 103 μm3 (19.4 pl). Functionality of the spectroscopic module of the prototype device is illustrated through the detection of 1Η resonance in deionized water. The acquired spectra depict combined NMR capability with AFM that may ultimately enable biophysical and biochemical studies at the single cell level.

MOS-capacitor-based ionizing radiation sensors for occupational dosimetry applications

Presented is the first accumulating capacitive radiation sensor for low-dose, long-term exposures observed in occupational dosimetry. The sensors capacitance-voltage curve undergoes a semi-permanent negative shift due to ionizing radiation. By measuring the change in capacitance at a given voltage in the depletion region, the ionizing radiation that has been present on the sensor can be extracted. In order to achieve the low dose resolution required (less than 100 μGy) for occupational dosimetry, parameters such as the oxide thickness and annealing conditions are optimized. The result for a 2 mm × 2 mm sensor is 1.6 fF per 100 μGy, a capacitance shift detectable with commercial electronics.

Thermoelectric energy scavenging with temperature gradient amplification

In this paper, we demonstrate the application of fluorocarbon evaporative cooling in thermoelectric energy scavenging. The fabrication and performance characterization of a prototype micro-device is presented. The device consists of a thermoelectric generator mounted on a silicon substrate and encapsulated in a poly(dimethylsiloxane) chamber with a flexible cover. By filling the chamber with a fluorocarbon liquid of low boiling point (34°C), we were able to increase the body heat contact harvested energy by 226% compared to a device encapsulated in air. The availability of a variety of fluorocarbon liquids with different boiling points allows this harvesting amplification scheme to be used in a wide range of applications.

Temperature and concentration dependent fibrillogenesis for improved magnetic alignment of collagen gels

Collagen fibrils form the structural basis for a broad range of complex biological tissues and materials. Collagen serves as an ideal natural polymer, formed as gels or matrices, for engineering solutions aimed at the regeneration of tissues following damage or disease. Recapitulation of native tissue hierarchical structure involves the careful consideration of the fibril-microstructure of the target tissue extracellular matrix and the choice of fibrillogenesis conditions that favor spatially-dependent fibril alignment. While magnetic fields non-destructively influence collagen fibrillogenesis and alignment, previous methods have demonstrated only limited control, especially when preparing large volume tissue constructs suitable for implantation. In this study, we investigate the use of temperature-controlled fibrillogenesis over a range of applicable collagen concentrations for improved magnetic alignment of polymerizable collagen-fibril gels. Magnetically aligned collagen gels show that bulk and microscale fibril alignment depend on both polymerization temperature and collagen concentration. The degree of fibril alignment at the microscale increased with decreasing polymerization temperature and collagen concentration. Further, computational simulations suggest that lower polymerization temperatures affect the internal gel temperature distribution and convective fluid velocity, potentially facilitating greater fibril alignment. This work demonstrates improvements in observed fibril anisotropy compared to previous work using similar magnetic field strengths, suggesting that temperature and collagen concentration may be utilized to achieve desired fibril alignment and structural properties. Improved control of collagen-based gel structure may better emulate native tissue structural (alignment) and physical properties, with enhanced potential for repair success in vivo.