Microelectronic Device for Individual Cell Sorting

The biochip system developed within the project has a great potential for cell analysis, for research, diagnostic and therapeutic applications. Never before have scientists been able to individually control cells in a sample of several thousands. The system developed allows manipulating step by step from 1 to thousands of individual cells/beads in a sample as little as few microliters. In the research filed, biologists may be able to study cell-cell interaction with a precise control on the timing, use the chip for isolating fluorescently labelled cells from a small cell-load, or program the system to make complex interactions which might involve, for example, beads, liposomes, cells. In the diagnostic field, the system could be used to isolate rare-cells from pre-processed samples, in particular it could be the only system affording the possibility to isolate 10-100 cells (too many for manual operation, and more reliable than that) from a population of 10,000-100,000 (too small for Fluorescent Activated Cell Sorters). Also, due to the integration of sensors, the MeDICS technology could implement a low-cost device for Point-of-Care blood cells analysis, once coupled with some sample collection and preparation stages. More information on the MEDICS project can be found at: http://www.siliconbiosystems.com/MeDICS/

Label-free cell separation based on cells physical properties such as size and dielectric signatures has been demonstrated. This approach could turn to be useful for sample preparation before genetic analysis in a number of sectors. Among these, we could cite forensics, diagnostics and theranostics. More information on the MEDICS project can be found at: http://www.siliconbiosystems.com/MeDICS/

Leti/CEA has developed different low temperature solutions for sealing the fluidic component of the chip to the silicon surface and which allows great flexibility in the fluidic circuit designs and in the choice of hybrid materials. Either solution may be used either for individual prototyping or for collective fabrication. The first solution is a method to seal structured substrates by depositing a hermetic glue gasket on the top of the walls of the micro-fluidic components (channels, chambers, wells). The process avoids filling the cavities with glue and has the following advantages: - It can accommodate any hybrid material bonding (silicon, glass, or polymer); - It is a low temperature process (the exact temperature is dependent on the curing mode) and it is therefore compatible with a wide range of polymers; - It is compatible with pre-functionalised devices (such as chemical or biological grafting); - It is compatible with high temperature uses (and has been validated in a thermal cycling PCR polymer fluidic device); - It is compatible with thin structures such as channels (validated down to 30µm wide channels); - It is compatible with individual and collective fabrication methods(validated on 4'' wafers). The other solution uses laser ablated preformed double sticky tape. The gasket forms the fluidic circuit and brings hermetical bonding in a unique operation. This is particularly suited for large scale channels (minimum channel width = 300µm) and dismountable devices. This allows the polymer fluidic part to be disposable while the active more expensive silicon part is re-usable. More information on the MEDICS project can be found at: http://www.siliconbiosystems.com/MeDICS/

ITO is the most widely used transparent electrode. It is an inorganic layer deposited mainly on glass using high temperature process deposition which is widely used in opoelectronics devices and more specifically for flat display (LCD, FED). This commercial ITO is mainly available on planar glass substrates, the deposition process can then use a high temperature annealing step to crystallize the ITO deposited layer. With the evolution of large display to organic materials (OLED), polymer substrates are beginning to be used so a considerable research effort has been made to deposit low temperature ITO on polymer foils used for the OLED technology (PET, PC for example) but this process is still at a development stage and not commercially available. The ITO specification chart for OLED applications lead to a deposition process compatible with planar substrates, the key parameter for this application being an optimised transparency in the visible spectrum. For bio-fluidic applications where the detection is very often optical observation or measurement, ITO is also the best candidate as a transparent electrode. In this field of applications pulled by the need of low cost disposable devices, the last years have seen a strong development of polymeric microsystems complementarily with well established silicon and glass micro-devices. It can be foreseen that for the production of large volume, low cost disposable devices (for diagnosis for example) replicated polymer micro-fluidic devices would be the commercial efficient solution. Therefore there is a need of a low temperature ITO process compatible with polymer micro-system production (ie. with non planar substrates), optimised foremost for its electrical characteristics and, to a second extent, for its optical transparency. In the Medics device, the observation of cell manipulation is done using an optical fluorescence microscope through the fluidic cap. The cap therefore has to be transparent for visible light and non fluorescent. A counter electrode deposited on the fluidic cap is used to create the DEP field. So this electrode has also to fulfil the transparency requirement for cell observation. Biological and fluidic compatibilities have to be respected. Thus we had to develop a specific process to fulfil our requirements: - A low temperature ITO process, compatible with polymer substrates (Tmax < 150°C); - Deposition on a non planar substrate keeping an electrical continuity of the ITO layer at the vertical edges; - Compatibility of ITO layer with the biologic liquids; - Good electrical characteristics for DEP. The deposition is made using a DC magnetron sputtering process in an MRC equipment. In this equipment the samples to be covered are moved above the target, the translation speed giving the thickness of the layer. This translation also leads to different deposition incidence angles of the species on the substrate and gives very good covering characteristics on a vertical plane. Electrical characteristics of the ITO layer are given by the layer's crystalline / amorphous structure and thickness. The higher thicknesses lead to lower sheet resistance but also to lower optical transmission. Another difficulty is the mechanical behaviour of the ITO layer on the polymeric substrate. Polymers have a much higher dilatation coefficient than the ITO inorganic layer, so the temperature crystallisation step of the ITO induces stress in the ITO layer, which can generate cracks and adhesion failure. This effect is enhanced when the layer is in contact with liquids: either alcohol for the cleaning and sterilization protocols or aqueous solutions used for the biological experiments. We have developed a process, which gives unreached electrical and optical qualities of ITO on polymer as well as exceptional mechanical adhesion behaviour of the ITO layer on a polymer surface. Stabilized Results: - ITO layer characteristics on Polycarbonate (PC) and a SU8 photoresist. - Rsq= 25-30Wsq or a R=4 10-4 Ohm.cm. - Optical transmission > 90% in the visible range. - With a lifetime in biological fluid conditions (ie no cracks or adhesion failure) > 30 days. This layer also shows no damage after the dicing step, allowing a complete collective fabrication process of the fluidic caps. The process has been developed and validated on a 4¿¿ wafer. More information on the MEDICS project can be found at: http://www.siliconbiosystems.com/MeDICS/

Leistungen

Diese Seite teilen

Herunterladen