Patent FR-2933198-A1 (FR)
Title: Fabricating biosensor on semiconductor wafer, by preparing central photosensitive area comprising a pixel device, covering first peripheral area by hydrophilic surface, and covering central photosensitive area by hydrophobic surface
Inventor: RAYNOR JEFFREY M
IPC: G01N33/543
Filed: 2008-06-27
Abstract: The process comprises preparing a central photosensitive area comprising a pixel device for biological analysis with a photosensitive layer and a first peripheral area surrounding the central photosensitive area comprising electronic circuits, covering the first peripheral area by a hydrophilic surface, and covering the central photosensitive area by a hydrophobic surface of which the roughness is chosen so that a dose of a solution is deposited on the central photosensitive area without spreading beyond the area to reach the first peripheral area. The process comprises preparing a central photosensitive area comprising a pixel device for biological analysis with a photosensitive layer and a first peripheral area surrounding the central photosensitive area comprising electronic circuits, covering the first peripheral area by a hydrophilic surface, covering the central photosensitive area by a hydrophobic surface of which the roughness is chosen so that a dose of a solution is deposited on the central photosensitive area without spreading beyond the area to reach the first peripheral area, and forming a barrier of a biocompatible resin on the second peripheral area. The resin is naturally fixed, before polymerization, on the hydrophilic surface without spreading on the hydrophobic surface. The process further comprises preparing an electrical contact connected to electronic circuits of the first peripheral area in a second peripheral area surrounding the first peripheral device, and covering the second peripheral area by a hydrophobic surface. A step of depositing a capturing mixture comprising a probe protein grafted by a hydrogel is carried out on the surface of the photosensitive layer of the device for biological analysis of pixel coated by hydrophobic surface for capturing target proteins. The step of depositing the capturing mixture comprises preparing (S100, S102, S104, S106, S108, S110) an outer surface of the photosensitive layer for receiving the capturing mixture and then silanizing the outer surface, oxidizing the hydrogel and then grafting the oxidized hydrogel on the silanized outer surface, carboxylating and then activating the grafted hydrogel, and grafting the probe protein in the activated hydrogel. The preparation step of the external surface by silanization comprises cleaning of the outer surface by successive rinsing in purified water in acetone and absolute ethanol in an ultrasonic bath, performing alkaline oxidation of the outer surface by oxidation under the action of a plasma ozone and then treating by a potassium hydroxide solution for several hours at room temperature, successively immersing the surface in purified water and then in absolute ethanol under ultrasound and drying under argon flux, silanizing the external surface by 3-aminopropyltriethoxysilane solution in ethanol for several hours, successively immersing in purified water in absolute ethanol under ultrasounds and drying under argon flux, and heating the device for several hours and then maintaining under an inert atmosphere. The oxidization and grafting of hydrogel comprises dissolving hydrogel in purified water and then treating by sodium periodate solution of which the volume is adjusted to obtain a mixture of which the molar ratio (50%) between sodium periodate and a predetermined and repeated monomer unit of hydrogel, protecting the reaction mixture obtained against the light and stirring for several hours at room temperature to obtain an oxidized hydrogel, grafting the oxidized hydrogel on the silanized external surface and stirring at room temperature and under light for several hours, treating the entire set obtained by an aqueous solution of sodium cyanoborohydride for several hours to reduce the formation of Schiff bases and then rinsing with purified water, ethanol, and drying under argon flux. The carboxylation and activation step of grafted hydrogel comprises treating hydrogel grafted by a bromoacetic acid solution in the sodium periodate for several hours at room temperature and under argon, purging the obtained reaction mixture and then rinsing with purified water, ethanol and drying under argon flux, and activating the formed carboxylate residues under ester and then rinsing in water. The external surface of the photosensitive layer of the pixel device is sized to have a surface of 25500x 10 -> 1> 2>m 2>, so that it corresponds to the size of a predetermined dose of a capturing mixture, which is placed on the outer surface as a drop. A unit is arranged for collecting photoelectrons comprising many collection areas conformed in islets, and spaced from each other in the photosensitive layer. The collecting areas are spaced from each other by a distance less than a maximum predetermined distance and fixed according to a distance of recombination of photoelectrons emitted in the photosensitive layer. The photosensitive layer is made to have a first portion capable of detecting an incident light intensity from a capturing mixture and intended to provide a first electrical magnitude and a second portion protected against the incident light intensity from the capturing mixture, intended to provide a second electrical magnitude. The step of forming central photosensitive area comprises forming a matrix for pixel devices in a central photosensitive area for biological analysis, each comprising a photosensitive layer, and forming an insulating gasket between adjacent pixels. The insulating gasket is shaped for electrically insulating a photosensitive layer of a pixel of the photosensitive layer of the adjacent pixel. An analog digital converter is arranged for converting a numerical data of a value characteristic of a light intensity detected by the pixel.