Victor Donald Samper

A novel 3D mammalian cell perfusion-culture system in microfluidic channels

Mammalian cells cultured on 2D surfaces in microfluidic channels are increasingly used in drug development and biological research applications. These systems would have more biological or clinical relevance if the cells exhibit 3D phenotypes similar to the cells in vivo. We have developed a microfluidic channel based system that allows cells to be perfusion-cultured in 3D by supporting them with adequate 3D cell-cell and cell-matrix interactions. The maximal cell-cell interaction was achieved by perfusion-seeding cells through an array of micropillars; and 3D cell-matrix interactions were achieved by a polyelectrolyte complex coacervation process to form a thin layer of matrix conforming to the 3D cell shapes. Carcinoma cell lines (HepG2, MCF7), primary differentiated (hepatocytes) and primary progenitor cells (bone marrow mesenchymal stem cells) were perfusion-cultured for 72 hours to 1 week in the microfluidic channel, which preserved their 3D cyto-architecture and cell-specific functions or differentiation competence. This transparent 3D microfluidic channel-based cell culture system also allows direct optical monitoring of cellular events for a wide range of applications.

Fabrication of a gecko-like hierarchical fibril array using a bonded porous alumina template

We report a new method to fabricate a hierarchical microfibril array by using bonded porous alumina templates. The fabrication approach extends a powerful and well-established technique of creating porous alumina to create a polymer multilevel structure, mimicking the hierarchical structure of gecko adhesive foot hairs. The nanoporous alumina (pore diameter ≈60 nm; interpore distance ≈100 nm) was generated by the anodization of an aluminum film in an oxalic acid solution. The microporous alumina was produced by exploiting the parallel wafer-scale processing of conventional lithography and anisotropic chemical etching of the thick film of anodic alumina pores. The micro- and nanoporous alumina membranes were subsequently brought into intimate contact and their bonding was accomplished by means of capillary forces and then van der Waals bonding. Hierarchical polymeric microfibrils (fibril diameter ≈10 µm; fibril length ≈70 µm) with nanofibril arrays at their tips were obtained after depositing a desired material into the pores and selective etching of the template membranes. The nanofibril has a lateral dimension of approximately 60 nm with length-to-diameter aspect ratios as high as 100:1.

Microfluidic reactor geometries for radiolysis reduction in radiopharmaceuticals

Autoradiolysis describes the degradation of radioactively labeled compounds due to the activity of the labeled compounds themselves. It scales with activity concentration and is of importance for high activity and microfluidic PET tracer synthesis. This study shows that microfluidic devices can be shaped to reduce autoradiolysis by geometric exclusion of positron interaction. A model is developed and confirmed by demonstrating in-capillary storage of non-stabilized [(18)F]FDG (2-[(18)F]Fluoro-2-deoxy-d-glucose) at max. 23 GBq/ml while maintaining >90% radiochemical purity over 14 h.

A solvent resistant lab-on-chip platform for radiochemistry applications

The application of microfluidics to the synthesis of Positron Emission Tomography (PET) tracers has been explored for more than a decade. Microfluidic benefits such as superior temperature control have been successfully applied to PET tracer synthesis. However, the design of a compact microfluidic platform capable of executing a complete PET tracer synthesis workflow while maintaining prospects for commercialization remains a significant challenge. This study uses an integral system design approach to tackle commercialization challenges such as the material to process compatibility with a path towards cost effective lab-on-chip mass manufacturing from the start. It integrates all functional elements required for a simple PET tracer synthesis into one compact radiochemistry platform. For the lab-on-chip this includes the integration of on-chip valves, on-chip solid phase extraction (SPE), on-chip reactors and a reversible fluid interface while maintaining compatibility with all process chemicals, temperatures and chip mass manufacturing techniques. For the radiochemistry device it includes an automated chip-machine interface enabling one-move connection of all valve actuators and fluid connectors. A vial-based reagent supply as well as methods to transfer reagents efficiently from the vials to the chip has been integrated. After validation of all those functional elements, the microfluidic platform was exemplarily employed for the automated synthesis of a Gastrin-releasing peptide receptor (GRP-R) binding the PEGylated Bombesin BN(7-14)-derivative ([(18)F]PESIN) based PET tracer.

Azeotropic drying free [18F]FDG synthesis and its application to a lab-on-chip platform

A very simple and time-saving cartridge-based drying technique for [(18)F]fluoride allows for an efficient [(18)F]FDG synthesis using protic solvents and high water content. This novel method has been adapted to a lab-on-chip synthesis platform mitigating the standard azeotropic drying process and demonstrating a proof of concept towards reduced hardware complexity for such systems.

Development of an anatomic heart model for the minimally-invasive closure of the left atrial appendage

The catheter based minimally-invasive closure of the left atrial appendage for stroke prevention can be realized by placing foldable structures in the heart with the help of a catheter. As a platform for the development and the evaluation of new devices, a phantom was developed that allows to perform the intervention under realistic imaging conditions. The centerpiece of the phantom is an anatomical correct hollow two chamber silicone heart model that offers the possibility to insert and unfold the occlusion device inside the left atrial appendage. The model is compatible with two and three dimensional ultrasound and fluoroscopy imaging. Untrained test persons were asked to perform the intervention and it could be concluded that one of the critical points of the procedure is to predict the implant position after the unfolding of the device.