Micro/NanoHerramientas para Aplicaciones a Celulas Vivas

Abstract

Micro/Nano-Electro-Mechanical Systems (MEMS/NEMS) applications for in vivo cell studies open a wide range of new applications in medicine, biology, and biochemistry. This has lead to develop devices for local drug delivery, microneedles for DNA injection, and micronozzles for cell holding among others.<br/>The work presented in this manuscript is framed within two projects: MINAHE and MINAHE II. The main goal of MINAHE was the development of technologies suitable for fabrication of micro/nano tools. Tools fabricated under MINAHE has found application in gold surface patterning and sub-picoliter dosage driven by an Atomic Force Microscope. MINAHE II employed these micro/nano tools on cellular applications.<br/>Following the current integration trend in microelectronics, two different integrative technologies have been developed and will be discussed here. The first technology presented is based on Microsystems technology combined with Focused Ion Beam (FIB) nanomilling. The fabricated device has been fitted to an Atomic Force Microscopic (AFM) for gold surface patterning. Experience developed in the first generation of micro/nano dispensers promoted a number of upgrades to produce a new generation of dispensers with emphasis for application in the Life Sciences. <br/>Technological processes were developed from component definition to back-end fabrication. Microchannel were defined on- substrate with micronozzles at the tip. The whole ensemble had AFM chip dimensions. This design favoured the use of microchannels as micro/nanodispensors and could effectively be used as surface functionalization tools. Once the components were identified, fabrication processes took place at Instituto de Microelectrónica de Barcelona, INM-CNM (CSIC) Clean Room (100-10000) facilities. First generation of micro/nanodispensers has sucessfully formed Self Assambled Monolayers (SAM). <br/>Experience developed in the first generation micro/nanodispensers promoted a number of upgrades to produce a Second generation of dispensers with an emphasis for applications in the Life Sciences. Transparent new devices were defined with specific shapes for cell manipulation. Anisotropic etching was replaced by Dry Reactive Ion Etching (DRIE) for improved process control. Packaging was improved with anodic bonding between silicon and glass chips and individual chip yield was increased by manual cleaving instead of wafer dicing. Transparent wall micro/nanodispensers would be designed due to biological application. To avoid lysis (cellular damage) or broken nozzles, some nozzles were designed sharply, in order to pierce wall and membrane surrounding live cells. FIB nanomachined render this type of nozzle. <br/>A crucial advantage in MEMS technology is versatility and monolithic integration. MEMS versatility can yield different devices although using the same technological process. We took advantage of this feature and manufactured microelectrodes, microfilters and micromixers as well. <br/>As a conclusion, it is worth emphasizing that research in this work range from micro/nanotechnologies to chemistry and biology. The first generation fabricated technology successfully formed SAM over gold surfaces. The second generation pierced walls and membranes in live cell. These devices present quite some advantages compared to conventional glass capillary. The proposed technology allows extreme definition of sizes and shapes in order not to damage cells. Microelectrodes fabricated will be tested inside a neuron cell to record electrical measurements. Work to develop this new application is still in progress.