Microfabrication

Résumé

alt=Micro-sculpture - Microlight3D|vignette|La « plus petite sculpture du monde », micro-autoportrait de l'artiste plasticien Michel Paysant imprimé en 3D avec une machine utilisant la technique de polymérisation à deux photons. La microfabrication est l'ensemble des techniques de fabrication permettant de produire des dispositifs avec des structures de l'ordre du micromètre et en dessous. En général on distingue les techniques de microélectronique et ses dérivés, utilisés par exemple pour la fabrication des puces électroniques, des microsystèmes et des diodes laser, et les autres techniques dérivant des techniques d'usinage traditionnelles. Pour les techniques de fabrication dérivant de la microélectronique, des plaquettes de silicium sont généralement utilisés comme substrat. On structure ensuite le dispositif par une succession d'étapes de dépôt et de mise en forme par photolithographie et gravure sèche ou humide. Certaines entreprises, comme Alvéole (entreprise), utilisent la ph

Source officielle

https://fr.wikipedia.org/wiki/Microfabrication

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Chargement

A Microfluidic Brain Interface for In Vivo Recording of Neurochemical Activity

Guillaume Cédric Yves Petitpierre

Neurological disorders have a strong negative impact on the quality of life of affected patients, their close relatives as well as on the health economic system. Early diagnosis associated with better treatment outcomes remain difficult to reach. Similarly, misdiagnosis is frequent and can lead to the delivery of the wrong treatment to the patient. As a matter of fact, the therapeutic strategies developed to treat Alzheimer's Disease (AD) and Parkinson's Disease (PD), two major neurodegenerative diseases, are unfortunately only effective for reducing the symptoms. This illustrates the lack of complete understanding of the mechanisms underlining neurodegeneration. In this context, this thesis aims to contribute to a precise comprehension of the synaptic transmission, at the cellular level, by providing a biocompatible brain interface capable of collecting neurochemicals while establishing a tight electrical connection with the cerebral tissues. The first part of this thesis deals with the design and microfabrication of a novel neural probe which includes microelectrodes and a micro-scale droplet generator for the efficient collection of extracellular fluid. The design choices and the microfabrication approach are detailed while the behavior of the device is assessed using fluidic modeling. Experimental results regarding the neural probe's mechanical strength, electrical and fluidic functions are then presented. In particular, the electrode-tissue interface is assessed using impedance spectroscopy. The probe fluidic function and its ability to perform high frequency (6Hz) droplet segmented collection in a rapidly changing environment is experimentally demonstrated. In a second phase is reported the successful in vivo testing of the neural probe in the framework of a pilot animal trial performed on rats. A custom microfabricated analysis platform enabling to efficiently detect the content of the collected brain fluid samples is presented as well. In particular a microfabricated target plate for the distribution and handling of the segmented samples during analysis is reported. This unique approach allows to maintain the temporal history of the flow-segmented samples. Combined with Inductively Coupled (ICP) Mass Spectrometry (MS), the detection results show the presence in significant quantity of Na, Mg, K and Ca, reflecting the neurochemical state of the brain over time. Quantitative measurements are demonstrated, highlighting the power of this approach. Simultaneous cerebral tissues electrical modulation and neurochemical recording during periods of 15 min is demonstrated in a third phase. A significant neurochemical response is detected in correlation with the electrical stimulation periods (2 x 1 min). In particular, the extracellular K+ ion concentration appears to rise during these periods which is further confirmed on each of the 3 implanted subjects. It is stated that the electrical stimulation delivered to the tissues set the neurons in a permanent hyperpolarized state, forcing a strong K+ ions efflux towards the extracellular space. This work sets a basis for the development of novel approaches in the detection of malfunction in synaptic transmission. Future perspectives of this technology include new methods enabling earlier diagnosis of neurodegenerative diseases and more efficient treatments based on a closed-loop adjustment of electrical stimulation.

EPFL2017

Chargement

Breakthroughs in health care over the coming decades may well consist of cell based therapeutics, potentially allowing the repair and replacement of damaged tissues and organs. Recently developed induced pluripotency methods as well as advances in stem cell biology show hope of such a reality. But such prospects come with the need to have a robust understanding and control over cell development and differentiation processes. Cells in the body develop in tightly controlled and specialized micro-environments that provide many complex cues and interactions that guide cell fate by directing gene expression. But current cell culture techniques that are most widely used to study the cell outside the body have not significantly changed from when first started over a century ago, using simple containers and flasks with plastic surfaces. Many studies have shown that three-dimensions (3D) over conventional 2D cell culture alone, showed to have increased levels of cell organization, morphology and function. By combining novel biomaterials and microfabrication methods, this project aims to create a tool that allows the study of cells within a simplified 3D environment. With the potential to build up the physical and soluble complexity of this environment in a tailor made fashion, a "dissection" of the functions and influences of external factors may be understood. Such a tool can also be used for the development of cell based models, highly relevant for drug discovery application as well as potentially for the development of cell based therapeutics. We have developed a novel microfluidic 3D cell culture platform that allows controlled soluble factor perfusion in an enzymatically formed and cell responsive PEG-based hydrogel. Soft lithographic processes were used to mold microchannels on a layer of hydrogel. In a second step, a flat hydrogel layer is placed on top to enclose and form the microchannels . The system allows the control over soluble factor delivery and it is able to perform long-term cell culture and generate user controlled gradients of soluble factors. With continuous perfusion, metabolic waste is constantly removed and cells are supplied with fresh medium. The platform also can allow creation of tailor made environments building up complexity in a controlled fashion. Higher throughput is also achieved by arraying individual culture chambers. The device was applied towards the culture of mouse embryonic stem cells (mESC) in order to demonstrate their self-renewal capacity on the microfluidic platform. The effects of some cytokine factors were also studied. Meaningful readouts such as fluorescence are easily used for analysis and cells can possibly be extracted from the device for further downstream analysis and processing. Through this device we show that microfluidics technologies combined with biomaterials enables the creation of platforms that are biologically relevant for the study and understanding of cell processes from cancer to stem cell development, processes which are fundamentally regulated by interactions with the microenvironment. The platform developed may also be used to develop human tissue models perhaps more relevant than current animal based testing, providing new tools for drug development and also potentially new approaches for developing cell based therapeutics

2009

Chargement

Fabrication of solid-state Nanopores for DNA analysis

Maïté Volatier

One of revolutionary technologies to sequence single molecules, such as DNA, is using nanopore devices. A single-channel with nanometer-scale aperture allows an extremely rapid electric analysis of such single molecules. The objective of this work is to fabricate nanopores into robust, solid-state membranes to achieve better performances. The technological challenge is in the small required dimension of the nanopore, around 50-100 nm in diameter and depth. To reach this objective, we used two different techniques: the ion track technique and a microfabrication method associated with Focused Ion Beam (FIB). A literature review has been done on the ion track technique. Threshold values of the ion track formation have been found for different insulator materials (polymers, SiO2, SiN). We did experiments with the linear accelerator UNILAC (Universal Linear Accelerator) at the GSI (Darmstadt, Germany) where we irradiated our samples with heavy gold ions (11.4 MeV/nucleon). On very thin membranes, we expect that a direct perforation would occur, and we chose SiN membranes and SU-8 thin films as samples. However, the experiment of ion bombardment was not possible to be done early enough, thus TEM analysis have not been done yet. If the direct perforation by ion bombardment is not possible, a chemical etching step would be necessary. About the microfabrication method associated with Focused Ion Beam (FIB) perforation, we did experiments at the Center of Micro Nano Technology (CMI) in EPFL. First trial with FIB was done on SiN membranes. In order to obtain required aperture size, reduction of membrane thickness before perforation by FIB was attempted, but this process was difficult to be achieved because of charging. To overcome this dimension limitation we chose a silicon membrane. With silicon membranes, oxidation would be performed after perforation by FIB, since channel opening will be reduced by SiO2 growth. Moreover, this oxide layer allows a functionalisation of the inner surface of the nanopore by silane chemistry. That should improve the resolution of DNA analysis. Though the aperture size reduction by oxidation has not been done yet, refining and perforation by FIB will be done according to this idea. We should reach ca. 100 nm-aperture size. Even if validation measurements are not easy, our specifications should be reached with the oxidation. More experiments and analysis have to be performed for further improvement.

2004

Chargement

A Microfluidic Brain Interface for In Vivo Recording of Neurochemical Activity

Guillaume Cédric Yves Petitpierre

EPFL2017

2009

Fabrication of solid-state Nanopores for DNA analysis

Maïté Volatier

2004